中文版 | English
Title

拟南芥 Dicer 家族蛋白 DCL3 的结构功能研究

Alternative Title
STRUCTURAL AND FUNCTIONALSTUDIESOF THE DICER FAMILY PROTEIN DCL3 IN ARABIDOPSIS
Author
Name pinyin
Wang Qian
School number
11930849
Degree
博士
Discipline
0710 生物学
Subject category of dissertation
07 理学
Supervisor
杜嘉木
Mentor unit
生物系
Tutor units of foreign institutions
南方科技大学
Publication Years
2022-05-12
Submission date
2022-06-27
University
南方科技大学
Place of Publication
深圳
Abstract

在真核生物中,小RNA可以在转录水平或转录后水平开展基因调控,影响着生物体内基因的表达、抗病毒以及基因组稳定性维持等重要生物学过程。在小RNA的生物合成中,需要一类保守的具备“分子尺”功能的Dicer家族核酸内切酶,它能特异性地从前体RNA的一端测量特定长度,继而切割产生特定大小的小RNA,其对小RNA的产生起着决定性的作用。尽管前期已经研究建立了Dicer的整体结构模型,但其具体的活性切割机制,包括RNA的长度测量、末端特异性识别、切割位点确定,以及不对称切割机理,仍然有很多的未知之处,这很大程度上限制了我们对Dicer切割产生小RNA的原理的了解。

拟南芥中有四种不同的Dicer家族蛋白,分别为DICER-LIKE PROTEIN 1 (DCL1)DCL2DCL3DCL4,对应切割产生21-nt miRNA22-nt siRNA24-nt siRNA21-nt siRNA。其中,在植物特有的RNA指导的DNA甲基化(RdDM)途径中,Dicer家族酶DCL3Pol IVRDR2产生的前体siRNApre-siRNA)特异性地切割至24-bp,其中由Pol IV所产生的24-nt链特异性装载入下游AGO4中,进一步与Pol V转录的长链非编码RNA互作,介导下游的DNA甲基化。为理解植物中24-nt siRNA的生物合成机制,我们对DCL3开展了结构和功能的研究。

通过RNA优化、金属离子替换等手段,本研究捕获了DCL3的活性形式,通过冷冻制样、电镜数据采集,以及冷冻电镜结构测定等实验过程测定了DCL3和底物RNA在活性状态下的复合物结构,直观地展示了DCL3处于正在切割状态下的分子机制:确定了DCL3利用两个不同结合口袋分别识别5'端磷酸化A13'1个碱基突出的分子基础;定位了RNaseIIIaRNaseIIIb将互补链和先导链分别切割为23-nt24-nt的两个活性位点;确定了platform-PAZ-connector区域和RNaseIII结构域间的距离决定Dicer分子标尺长度的机理;利用DCL3与非最适底物RNA复合物的结构,揭示了底物RNA通过第一个碱基对U1-A1'的双重翻转机制,以允许底物RNA互补链3'端具有更长的突出碱基。

整体上,本论文通过结构生物学、生物化学以及基因组RNA测序研究等方法揭示了DCL3产生24-nt siRNA的具体分子机制:5'端磷酸化偏好性、5'端碱基的选择、3'端突出识别、3'端突出容忍、高效活性切割、长度测量和动态切割的完整过程。Dicer家族蛋白的切割机制在动植物中非常保守,本研究也为其他物种,特别是人源Dicer的切割机制提供了参考。本研究不仅从分子层面系统分析了植物Dicer的微观作用机制,还为利用异源Dicer设计小RNA开展RNAi疗法等生物医学研究提供了新的思路。

Keywords
Language
Chinese
Training classes
独立培养
Enrollment Year
2019-09
Year of Degree Awarded
2022-06
References List

[1] MCKEOWN P C, SPILLANE C. Landscaping plant epigenetics [J]. Methods Molecular Biology, 2014, 1112: 1-24.
[2] HOLLIDAY R. Epigenetics A Historical Overview [J]. Epigenetics, 2006, 1(2): 76-80.
[3] BERGER S L, KOUZARIDES T, SHIEKHATTAR R, et al. An operational definition of epigenetics [J]. Genes Development, 2009, 23(7): 781-783.
[4] PECINKA A, MITTELSTEN SCHEID O. Stress-induced chromatin changes: a critical view on their heritability [J]. Plant and Cell Physiology, 2012, 53(5): 801-808.
[5] WANG J W, QI Y. Plant non-coding RNAs and epigenetics [J]. Science China Life Sciences, 2018, 61(2): 135-137.
[6] HAUSER M T, AUFSATZ W, JONAK C, et al. Transgenerational epigenetic inheritance in plants [J]. Biochimca et Biophysica Acta, 2011, 1809(8): 459-468.
[7] RAINA M, IBBA M. tRNAs as regulators of biological processes [J]. Frontiers in Genetics, 2014, 5: 171.
[8] XU X W, ZHOU X H, WANG R R, et al. Functional analysis of long intergenic non-coding RNAs in phosphate-starved rice using competing endogenous RNA network [J]. Scientific Reports, 2016, 6.
[9] WANG J J, MENG X W, DOBROVOLSKAYA O B, et al. Non-coding RNAs and Their Roles in Stress Response in Plants [J]. Genomics, Proteomics & Bioinformatics, 2017, 15(5): 301-312.
[10] DI C, YUAN J P, WU Y, et al. Characterization of stress-responsive lncRNAs in Arabidopsis thaliana by integrating expression, epigenetic and structural features [J]. Plant Journal, 2014, 80(5): 848-861.
[11] SONG X W, LI Y, CAO X F, et al. MicroRNAs and Their Regulatory Roles in Plant-Environment Interactions [J]. Annual Review of Plant Biology, Vol 70, 2019, 70: 489-525.
[12] AU P C, ZHU Q H, DENNIS E S, et al. Long non-coding RNA-mediated mechanisms independent of the RNAi pathway in animals and plants [J]. RNA Biology, 2011, 8(3): 404-414.
[13] LUCERO L, FONOUNI-FARDE C, CRESPI M, et al. Long noncoding RNAs shape transcription in plants [J]. Transcription, 2020, 11(3-4): 160-171.
[14] XU C, TIAN J, MO B. siRNA-mediated DNA methylation and H3K9 dimethylation in plants [J]. Protein Cell, 2013, 4(9): 656-663.
[15] HUANG Y, LI Y. Secondary siRNAs rescue virus-infected plants [J]. Nature Plants, 2018, 4(3): 136-137.
[16] SANAN-MISHRA N, ABDUL KADER JAILANI A, MANDAL B, et al. Secondary siRNAs in Plants: Biosynthesis, Various Functions, and Applications in Virology [J]. Frontiers in Plant Science, 2021, 12: 610283.
[17] KHRAIWESH B, ZHU J K, ZHU J. Role of miRNAs and siRNAs in biotic and abiotic stress responses of plants [J]. Biochimica et Biophysica Acta, 2012, 1819(2): 137-148.
[18] IWAKAWA H O, LAM A Y W, MINE A, et al. Ribosome stalling caused by the Argonaute-microRNA-SGS3 complex regulates the production of secondary siRNAs in plants [J]. Cell Reports, 2021, 35(13): 109300.
[19] WU L. DICER-LIKE1 processed trans-acting siRNAs mediate DNA methylation: case study of complex small RNA biogenesis and action pathways in plants [J]. Plant Signal & Behavior, 2013, 8(1): e22476.
[20] LI Y, DENG C, SHANG Q, et al. Characterization of siRNAs derived from cucumber green mottle mosaic virus in infected cucumber plants [J]. Archives of Virology, 2016, 161(2): 455-458.
[21] QIAO W, ZARZYNSKA-NOWAK A, NERVA L, et al. Accumulation of 24 nucleotide transgene-derived siRNAs is associated with crinivirus immunity in transgenic plants [J]. Molecular Plant Pathology, 2018, 19(10): 2236-2247.
[22] YANG X, ZHANG L, YANG Y, et al. miRNA Mediated Regulation and Interaction between Plants and Pathogens [J]. International Journal of Molecular Sciences, 2021, 22(6): 2913.
[23] SHAH S M S, ULLAH F. A comprehensive overview of miRNA targeting drought stress resistance in plants [J]. Brazilian Journal of Biology, 2021, 83: e242708.
[24] BOUBA I, KANG Q, LUAN Y S, et al. Predicting miRNA-lncRNA interactions and recognizing their regulatory roles in stress response of plants [J]. Mathematical Bioscience, 2019, 312: 67-76.
[25] ZHU L, OW D W, DONG Z C. Transfer RNA-derived small RNAs in plants [J]. Science China Life Science, 2018, 61(2): 155-161.
[26] GUTBROD M J, MARTIENSSEN R A. Conserved chromosomal functions of RNA interference [J]. Nature Reviews Genetics, 2020, 21(5): 311-331.
[27] CHEN C J, LI J W, FENG J T, et al. sRNAanno-a database repository of uniformly annotated small RNAs in plants [J]. Horticulture Research, 2021, 8(1): 45.
[28] GUO Z L, KUANG Z, WANG Y, et al. PmiREN: a comprehensive encyclopedia of plant miRNAs [J]. Nucleic Acids Research, 2020, 48(D1): D1114-D1121.
[29] STEPIEN A, KNOP K, DOLATA J, et al. Posttranscriptional coordination of splicing and miRNA biogenesis in plants [J]. Wiley Interdisciplinary Reviews: RNA, 2017, 8(3): e1403.
[30] CHO S K, RYU M Y, SHAH P, et al. Post-Translational Regulation of miRNA Pathway Components, AGO1 and HYL1, in Plants [J]. Molecules and Cells, 2016, 39(8): 581-586.
[31] FEI Q L, XIA R, MEYERS B C. Phased, Secondary, Small Interfering RNAs in Posttranscriptional Regulatory Networks [J]. Plant Cell, 2013, 25(7): 2400-2415.
[32] SANAN-MISHRA N, JAILANI A A K, MANDAL B, et al. Secondary siRNAs in Plants: Biosynthesis, Various Functions, and Applications in Virology [J]. Frontiers in Plant Science, 2021, 12: 610283.
[33] ALLEN E, XIE Z X, GUSTAFSON A I, et al. microRNA-directed phasing during trans-acting siRNA biogenesis in plants (Reprinted from Cell, vol 121, pg 207-221, 2005) [J]. Cell, 2007, 131(4): 74-88.
[34] AREGGER M, BORAH B K, SEGUIN J, et al. Primary and Secondary siRNAs in Geminivirus-induced Gene Silencing [J]. PLOS Pathogens, 2012, 8(9): e1002941.
[35] CUPERUS J T, CARBONELL A, FAHLGREN N, et al. Unique functionality of 22-nt miRNAs in triggering RDR6-dependent siRNA biogenesis from target transcripts in Arabidopsis [J]. Nature Structural & Molecular Biology, 2010, 17(8): 997-1003.
[36] AXTELL M J. Classification and comparison of small RNAs from plants [J]. Annual Review of Plant Biology, 2013, 64: 137-159.
[37] BORGES F, MARTIENSSEN R A. The expanding world of small RNAs in plants [J]. Nature Reviews Molecular Cell Biology, 2015, 16(12): 727-741.
[38] SIMON S A, MEYERS B C. Small RNA-mediated epigenetic modifications in plants [J]. Current Opinion in Plant Biology, 2011, 14(2): 148-155.
[39] BORGES F, MARTIENSSEN R A. The expanding world of small RNAs in plants [J]. Nature Reviews Molecular Cell Biology, 2015, 16(12): 727-741.
[40] PALAUQUI J C, ELMAYAN T, DEBORNE F D, et al. Frequencies, timing, and spatial patterns of co-suppression of nitrate reductase and nitrite reductase in transgenic tobacco plants [J]. Plant Physiology, 1996, 112(4): 1447-1456.
[41] UDDIN M N, KIM J Y. Non-cell-autonomous RNA silencing spread in plants [J]. Botanical Studies, 2011, 52(2): 129-136.
[42] VOINNET O. Non-cell autonomous RNA silencing [J]. FEBS Letters, 2005, 579(26): 5858-5871.
[43] KALANTIDIS K, SCHUMACHER H T, ALEXIADIS T, et al. RNA silencing movement in plants [J]. Biology of the Cell, 2008, 100(1): 13-26.
[44] HENDERSON I R, ZHANG X, LU C, et al. Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning [J]. Nature Genetics, 2006, 38(6): 721-725.
[45] GASCIOLLI V, MALLORY A C, BARTEL D P, et al. Partially redundant functions of Arabidopsis DICER-like enzymes and a role for DCL4 in producing trans-acting siRNAs [J]. Current Biology, 2005, 15(16): 1494-1500.
[46] FUKUDOME A, FUKUHARA T. Plant dicer-like proteins: double-stranded RNA-cleaving enzymes for small RNA biogenesis [J]. Journal of Plant Research, 2017, 130(1): 33-44.
[47] HO T, WANG L, HUANG L, et al. Nucleotide bias of DCL and AGO in plant anti-virus gene silencing [J]. Protein&Cell, 2010, 1(9): 847-858.
[48] DALMADI A, GYULA P, BALINT J, et al. AGO-unbound cytosolic pool of mature miRNAs in plant cells reveals a novel regulatory step at AGO1 loading [J]. Nucleic Acids Research, 2019, 47(18): 9803-9817.
[49] ZHAI J X, BISCHOF S, WANG H F, et al. A One Precursor One siRNA Model for Pol IV-Dependent siRNA Biogenesis [J]. Cell, 2015, 163(2): 445-455.
[50] MATZKE M A, MOSHER R A. RNA-directed DNA methylation: an epigenetic pathway of increasing complexity (vol 15, 394, 2014) [J]. Nature Reviews Genetics, 2014, 15(8): 394-408
[51] HUNG Y H, SLOTKIN R K. The initiation of RNA interference (RNAi) in plants [J]. Current Opinion in Plant Biology, 2021, 61: 102014.
[52] ZHANG H M, LANG Z B, ZHU J K. Dynamics and function of DNA methylation in plants [J]. Nature Reviews Molecular Cell Biology, 2018, 19(8): 489-506.
[53] SUN T, ZHOU Q, ZHOU Z, et al. SQUINT Positively Regulates Resistance to the Pathogen Botrytis cinerea via miR156-SPL9 Module in Arabidopsis [J]. Plant Cell Physiology, 2022, pcac042.
[54] ZHOU Q, SHI J, LI Z, et al. miR156/157 Targets SPLs to Regulate Flowering Transition, Plant Architecture and Flower Organ Size in Petunia [J]. Plant Cell Physiology, 2021, 62(5): 839-857.
[55] CARLSBECKER A, LEE J Y, ROBERTS C J, et al. Cell signalling by microRNA165/6 directs gene dose-dependent root cell fate [J]. Nature, 2010, 465(7296): 316-321.
[56] NODINE M D, BARTEL D P. MicroRNAs prevent precocious gene expression and enable pattern formation during plant embryogenesis [J]. Genes & Development, 2010, 24(23): 2678-2692.
[57] MATZKE M A, MOSHER R A. RNA-directed DNA methylation: an epigenetic pathway of increasing complexity [J]. Nature Reviews Genetics, 2014, 15(6): 394-408.
[58] SLOTKIN R K, MARTIENSSEN R. Transposable elements and the epigenetic regulation of the genome [J]. Nature Reviews Genetics, 2007, 8(4): 272-285.
[59] YOSHIKAWA M, PERAGINE A, PARK M Y, et al. A pathway for the biogenesis of trans-acting siRNAs in Arabidopsis [J]. Genes & Development, 2005, 19(18): 2164-2175.
[60] AXTELL M J, JAN C, RAJAGOPALAN R, et al. A two-hit trigger for siRNA biogenesis in plants [J]. Cell, 2006, 127(3): 565-577.
[61] BOUCHE N, LAURESSERGUES D, GASCIOLLI V, et al. An antagonistic function for Arabidopsis DCL2 in development and a new function for DCL4 in generating viral siRNAs [J]. The EMBO Journal, 2006, 25(14): 3347-3456.
[62] CHEN D, MENG Y, MA X, et al. Small RNAs in angiosperms: sequence characteristics, distribution and generation [J]. Bioinformatics, 2010, 26(11): 1391-1394.
[63] GARCIA-RUIZ H, TAKEDA A, CHAPMAN E J, et al. Arabidopsis RNA-Dependent RNA Polymerases and Dicer-Like Proteins in Antiviral Defense and Small Interfering RNA Biogenesis during Turnip Mosaic Virus Infection [J]. The Plant Cell, 2010, 22(2): 481-496.
[64] GARCIA-RUIZ H, TAKEDA A, CHAPMAN E J, et al. Arabidopsis RNA-dependent RNA polymerases and dicer-like proteins in antiviral defense and small interfering RNA biogenesis during Turnip mosaic virus infection (vol 22, pg 481, 2010) [J]. The Plant Cell, 2015, 27(3): 944-945.
[65] QIN C, LI B, FAN Y Y, et al. Roles of Dicer-Like Proteins 2 and 4 in Intra- and Intercellular Antiviral Silencing [J]. Plant Physiology, 2017, 174(2): 1067-1081.
[66] CREASEY K M, ZHAI J, BORGES F, et al. miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis [J]. Nature, 2014, 508(7496): 411-415.
[67] ZHAI J, ZHANG H, ARIKIT S, et al. Spatiotemporally dynamic, cell-type-dependent premeiotic and meiotic phasiRNAs in maize anthers [J]. Proceedings of the National Academy of Sciences, 2015, 112(10): 3146-3151.
[68] DUKOWIC-SCHULZE S, SUNDARARAJAN A, RAMARAJ T, et al. Novel Meiotic miRNAs and Indications for a Role of PhasiRNAs in Meiosis [J]. Frontiers in Plant Science, 2016, 7: 762.
[69] TENG C, ZHANG H, HAMMOND R, et al. Dicer-like 5 deficiency confers temperature-sensitive male sterility in maize [J]. Nature Communications, 2020, 11(1): 2912.
[70] DUKOWIC-SCHULZE S, SUNDARARAJAN A, RAMARAJ T, et al. Corrigendum: Novel Meiotic miRNAs and Indications for a Role of PhasiRNAs in Meiosis [J]. Frontiers in Plant Science, 2020, 11: 653.
[71] CHEN H M, CHEN L T, PATEL K, et al. 22-nucleotide RNAs trigger secondary siRNA biogenesis in plants [J]. Proceedings of the National Academy of Sciences, 2010, 107(34): 15269-15274.
[72] XIE D, CHEN M, NIU J, et al. Phase separation of SERRATE drives dicing body assembly and promotes miRNA processing in Arabidopsis [J]. Nature Cell Biology, 2021, 23(1): 32-39.
[73] WERNER S, WOLLMANN H, SCHNEEBERGER K, et al. Structure determinants for accurate processing of miR172a in Arabidopsis thaliana [J]. Current Biology, 2010, 20(1): 42-48.
[74] SONG L, AXTELL M J, FEDOROFF N V. RNA secondary structural determinants of miRNA precursor processing in Arabidopsis [J]. Current Biology, 2010, 20(1): 37-41.
[75] MATEOS J L, BOLOGNA N G, CHOROSTECKI U, et al. Identification of microRNA processing determinants by random mutagenesis of Arabidopsis MIR172a precursor [J]. Current Biology, 2010, 20(1): 49-54.
[76] ZHU H, ZHOU Y, CASTILLO-GONZALEZ C, et al. Bidirectional processing of pri-miRNAs with branched terminal loops by Arabidopsis Dicer-like1 [J]. Nature Structural & Molecular Biology, 2013, 20(9): 1106-1115.
[77] MENG Y, SHAO C, WANG H, et al. Uncovering DCL1-dependent small RNA loci on plant genomes: a structure-based approach [J]. J Environmental and Experimental Botany, 2014, 65(2): 395-400.
[78] DONG Z, HAN M H, FEDOROFF N. The RNA-binding proteins HYL1 and SE promote accurate in vitro processing of pri-miRNA by DCL1 [J]. Proceedings of the National Academy of Sciences, 2008, 105(29): 9970-9975.
[79] WEI X, KE H, WEN A, et al. Structural basis of microRNA processing by Dicer-like 1 [J]. Nature Plants, 2021, 7(10): 1389-1396.
[80] MONTAVON T, KWON Y, ZIMMERMANN A, et al. Characterization of DCL4 missense alleles provides insights into its ability to process distinct classes of dsRNA substrates [J]. The Plant Journal, 2018, 95(2): 204-218.
[81] NAGANO H, FUKUDOME A, HIRAGURI A, et al. Distinct substrate specificities of Arabidopsis DCL3 and DCL4 [J]. Nucleic Acids Research, 2014, 42(3): 1845-1856.
[82] WU Y Y, HOU B H, LEE W C, et al. DCL2- and RDR6-dependent transitive silencing of SMXL4 and SMXL5 in Arabidopsis dcl4 mutants causes defective phloem transport and carbohydrate over-accumulation [J]. The Plant Journal, 2017, 90(6): 1064-1078.
[83] KAKIYAMA S, TABARA M, NISHIBORI Y, et al. Long DCL4-substrate dsRNAs efficiently induce RNA interference in plant cells [J]. Scientific Reports, 2019, 9(1): 6920.
[84] PARENT J S, BOUTEILLER N, ELMAYAN T, et al. Respective contributions of Arabidopsis DCL2 and DCL4 to RNA silencing [J]. The Plant Journal, 2015, 81(2): 223-232.
[85] QIN H, CHEN F, HUAN X, et al. Structure of the Arabidopsis thaliana DCL4 DUF283 domain reveals a noncanonical double-stranded RNA-binding fold for protein-protein interaction [J]. Rna, 2010, 16(3): 474-481.
[86] NAKAZAWA Y, HIRAGURI A, MORIYAMA H, et al. The dsRNA-binding protein DRB4 interacts with the Dicer-like protein DCL4 in vivo and functions in the trans-acting siRNA pathway [J]. Plant Molecular Biology, 2007, 63(6): 777-785.
[87] LOFFER A, SINGH J, FUKUDOME A, et al. A DCL3 dicing code within Pol IV-RDR2 transcripts diversifies the siRNA pool guiding RNA-directed DNA methylation [J]. Elife, 2022, 11: e73260.
[88] WENDTE J M, PIKAARD C S. The RNAs of RNA-directed DNA methylation [J]. Biochimica et Biophysica Acta-Gene Regulatory Mechanisms, 2017, 1860(1): 140-148.
[89] HUANG K, WU X X, FANG C L, et al. Pol IV and RDR2: A two-RNA-polymerase machine that produces double-stranded RNA [J]. Science, 2021, 374(6575): 1579-1586.
[90] BLEVINS T, PODICHETI R, MISHRA V, et al. Identification of Pol IV and RDR2-dependent precursors of 24 nt siRNAs guiding de novo DNA methylation in Arabidopsis [J]. Elife, 2015, 4: e09591.
[91] LI S, VANDIVIER L E, TU B, et al. Detection of Pol IV/RDR2-dependent transcripts at the genomic scale in Arabidopsis reveals features and regulation of siRNA biogenesis [J]. Genome Research, 2015, 25(2): 235-245.
[92] PIKAARD C S, HAAG J R, REAM T, et al. Roles of RNA polymerase IV in gene silencing [J]. Trends in Plant Science, 2008, 13(7): 390-397.
[93] SINGH J, MISHRA V, WANG F, et al. Reaction Mechanisms of Pol IV, RDR2, and DCL3 Drive RNA Channeling in the siRNA-Directed DNA Methylation Pathway [J]. Molecular Cell, 2019, 75(3): 576-589.
[94] ZILBERMAN D, CAO X, JACOBSEN S E. ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation [J]. Science, 2003, 299(5607): 716-719.
[95] MUKHERJEE K, CAMPOS H, KOLACZKOWSKI B. Evolution of Animal and Plant Dicers: Early Parallel Duplications and Recurrent Adaptation of Antiviral RNA Binding in Plants [J]. Molecular Biology and Evolution, 2013, 30(3): 627-641.
[96] WILLMANN M R, ENDRES M W, COOK R T, et al. The Functions of RNA-Dependent RNA Polymerases in Arabidopsis [J]. The Arabidopsis Book, 2011, 9: e0146.
[97] LU S, SHI R, TSAO C C, et al. RNA silencing in plants by the expression of siRNA duplexes [J]. Nucleic Acids Research, 2004, 32(21): e171.
[98] WEI L Y, GU L F, SONG X W, et al. Dicer-like 3 produces transposable element-associated 24-nt siRNAs that control agricultural traits in rice [J]. Proceedings of the National Academy of Sciences, 2014, 111(10): 3877-3882.
[99] DU Z, LEE J K, TJHEN R, et al. Structural and biochemical insights into the dicing mechanism of mouse Dicer: A conserved lysine is critical for dsRNA cleavage [J]. Proceedings of the National Academy of Sciences, 2008, 105(7): 2391-2396.
[100] PARENT J S, BOUTEILLER N, ELMAYAN T, et al. Respective contributions of Arabidopsis DCL2 and DCL4 to RNA silencing [J]. The Plant Journal, 2015, 81(2): 223-232.
[101] JIA J B, JI R H, LI Z W, et al. Soybean DICER-LIKE2 Regulates Seed Coat Color via Production of Primary 22-Nucleotide Small Interfering RNAs from Long Inverted Repeats [J]. The Plant Cell, 2020, 32(12): 3662-3673.
[102] DENIZ O, FROST J M, BRANCO M R. Regulation of transposable elements by DNA modifications [J]. Nature Reviews Genetics, 2019, 20(7): 417-431.
[103] ZHANG H, LANG Z, ZHU J K. Dynamics and function of DNA methylation in plants [J]. Nature Reviews Molecular Cell Biology, 2018, 19(8): 489-506.
[104] WASSENEGGER M, HEIMES S, RIEDEL L, et al. RNA-directed de novo methylation of genomic sequences in plants [J]. Cell, 1994, 76(3): 567-576.
[105] ZHANG X, YAZAKI J, SUNDARESAN A, et al. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis [J]. Cell, 2006, 126(6): 1189-1201.
[106] LAW J A, JACOBSEN S E. Establishing, maintaining and modifying DNA methylation patterns in plants and animals [J]. Nature Reviews Genetics, 2010, 11(3): 204-220.
[107] HAAG J R, REAM T S, MARASCO M, et al. In vitro transcription activities of Pol IV, Pol V, and RDR2 reveal coupling of Pol IV and RDR2 for dsRNA synthesis in plant RNA silencing [J]. Molecular Cell, 2012, 48(5): 811-818.
[108] WIERZBICKI A T, REAM T S, HAAG J R, et al. RNA polymerase V transcription guides ARGONAUTE4 to chromatin [J]. Nature Genetics, 2009, 41(5): 630-634.
[109] WIERZBICKI A T, HAAG J R, PIKAARD C S. Noncoding transcription by RNA polymerase Pol IVb/Pol V mediates transcriptional silencing of overlapping and adjacent genes [J]. Cell, 2008, 135(4): 635-648.
[110] ZHENG Z, XING Y, HE X J, et al. An SGS3-like protein functions in RNA-directed DNA methylation and transcriptional gene silencing in Arabidopsis [J]. The Plant Journal, 2010, 62(1): 92-99.
[111] AUSIN I, GREENBERG M V, SIMANSHU D K, et al. INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis [J]. Proceedings of the National Academy of Sciences, 2012, 109(22): 8374-8381.
[112] AUSIN I, MOCKLER T C, CHORY J, et al. IDN1 and IDN2 are required for de novo DNA methylation in Arabidopsis thaliana [J]. Nature Structural & Molecular Biology, 2009, 16(12): 1325-1327.
[113] LAHMY S, BIES-ETHEVE N, LAGRANGE T. Plant-specific multisubunit RNA polymerase in gene silencing [J]. Epigenetics, 2010, 5(1): 4-8.
[114] MOSHER R A, MELNYK C W, KELLY K A, et al. Uniparental expression of PolIV-dependent siRNAs in developing endosperm of Arabidopsis [J]. Nature, 2009, 460(7252): 283-286.
[115] JOHNSON L M, DU J, HALE C J, et al. SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation [J]. Nature, 2014, 507(7490): 124-128.
[116] JOHNSON L M, DU J, HALE C J, et al. Corrigendum: SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation [J]. Nature, 2017, 543(7643): 136.
[117] HENDERSON I R, JACOBSEN S E. Epigenetic inheritance in plants [J]. Nature, 2007, 447(7143): 418-424.
[118] LISTER R, O'MALLEY R C, TONTI-FILIPPINI J, et al. Highly integrated single-base resolution maps of the epigenome in Arabidopsis [J]. Cell, 2008, 133(3): 523-536.
[119] LAW J A, DU J, HALE C J, et al. Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1 [J]. Nature, 2013, 498(7454): 385-389.
[120] VAN DER KROL A R, MUR L A, BELD M, et al. Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression [J]. The Plant Cell, 1990, 2(4): 291-299.
[121] FIRE A, XU S, MONTGOMERY M K, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans [J]. Nature, 1998, 391(6669): 806-811.
[122] JIN L, CHEN M, XIANG M, et al. RNAi-Based Antiviral Innate Immunity in Plants [J]. Viruses, 2022, 14(2): 432.
[123] TRUNIGER V, ARANDA M A. Recessive resistance to plant viruses [J]. Advances in Virus Research, 2009, 75: 119-159.
[124] ABEL P P, NELSON R S, DE B, et al. Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene [J]. Science, 1986, 232(4751): 738-743.
[125] GUO Z, LI Y, DING S W. Small RNA-based antimicrobial immunity [J]. Nature Reviews Immunology, 2019, 19(1): 31-44.
[126] SZITTYA G, BURGYAN J. RNA interference-mediated intrinsic antiviral immunity in plants [J]. Current Topics in Microbiology and Immunology, 2013, 371: 153-181.
[127] MARTIENSSEN R, MOAZED D. RNAi and heterochromatin assembly [J]. Cold Spring Harbor Perspectives in Biology, 2015, 7(8): a019323.
[128] WASSENEGGER M, KRCZAL G. Nomenclature and functions of RNA-directed RNA polymerases [J]. Trends in Plant Science, 2006, 11(3): 142-151.
[129] VAZQUEZ F, LEGRAND S, WINDELS D. The biosynthetic pathways and biological scopes of plant small RNAs [J]. Trends in Plant Science, 2010, 15(6): 337-345.
[130] DING S W. RNA-based antiviral immunity [J]. Nature Reviews Immunology, 2010, 10(9): 632-644.
[131] DUNOYER P, MELNYK C, MOLNAR A, et al. Plant mobile small RNAs [J]. Cold Spring Harbor Perspectives in Biology, 2013, 5(7): a017897.
[132] BRUMMELKAMP T R, BERNARDS R, AGAMI R. A system for stable expression of short interfering RNAs in mammalian cells [J]. Science, 2002, 296(5567): 550-553.
[133] ZUCKERMAN J E, DAVIS M E. Clinical experiences with systemically administered siRNA-based therapeutics in cancer [J]. Nature Reviews Drug Discovery, 2015, 14(12): 843-856.
[134] MATHEW V, WANG A K. Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis [J]. Drug Design, Development and Therapy, 2019, 13: 1515-1525.
[135] SYED Y Y. Givosiran: A Review in Acute Hepatic Porphyria [J]. Drugs, 2021, 81(7): 841-848.
[136] FRESSIGNE L, SIMARD M J. Biogenesis of small non-coding RNAs in animals [J]. Medical Sciences, 2018, 34(2): 137-144.
[137] KIM V N, HAN J, SIOMI M C. Biogenesis of small RNAs in animals [J]. Nature Reviews Molecular Cell Biology, 2009, 10(2): 126-139.
[138] CARMELL M A, HANNON G J. RNase III enzymes and the initiation of gene silencing [J]. Nature Structural & Molecular Biology, 2004, 11(3): 214-218.
[139] HAMMOND S M. Dicing and slicing - The core machinery of the RNA interference pathway [J]. FEBS Letters, 2005, 579(26): 5822-5829.
[140] LEE Y S, NAKAHARA K, PHAM J W, et al. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways [J]. Cell, 2004, 117(1): 69-81.
[141] MACRAE I J, ZHOU K H, LI F, et al. Structural basis for double-stranded RNA processing by dicer [J]. Science, 2006, 311(5758): 195-198.
[142] KWON S C, NGUYEN T A, CHOI Y G, et al. Structure of Human DROSHA [J]. Cell, 2016, 164(1-2): 81-90.
[143] PARTIN A C, ZHANG K M, JEONG B C, et al. Cryo-EM Structures of Human Drosha and DGCR8 in Complex with Primary MicroRNA [J]. Molecular Cell, 2020, 78(3): 411-422.
[144] NGUYEN T A, JO M H, CHOI Y G, et al. Functional Anatomy of the Human Microprocessor [J]. Cell, 2015, 161(6): 1374-1387.
[145] SINHA N K, IWASA J, SHEN P S, et al. Dicer uses distinct modules for recognizing dsRNA termini [J]. Science, 2018, 359(6373): 329-334.
[146] MACRAE I J, MA E, ZHOU M, et al. In vitro reconstitution of the human RISC-loading complex [J]. Proceedings of the National Academy of Sciences, 2008, 105(2): 512-517.
[147] ZHANG H D, KOLB F A, JASKIEWICZ L, et al. Single processing center models for human dicer and bacterial RNase III [J]. Cell, 2004, 118(1): 57-68.
[148] PARK J E, HEO I, TIAN Y, et al. Dicer recognizes the 5' end of RNA for efficient and accurate processing [J]. Nature, 2011, 475(7355): 201-205.
[149] SINGH J, MISHRA V, WANG F, et al. Reaction Mechanisms of Pol IV, RDR2, and DCL3 Drive RNA Channeling in the siRNA-Directed DNA Methylation Pathway [J]. Molecular Cell, 2019, 75(3): 576-589. e5.
[150] MA E, MACRAE I J, KIRSCH J F, et al. Autoinhibition of human dicer by its internal helicase domain [J]. J Mol Biol, 2008, 380(1): 237-243.
[151] MACRAE I J, ZHOU K, DOUDNA J A. Structural determinants of RNA recognition and cleavage by Dicer [J]. Nature Structural & Molecular Biology, 2007, 14(10): 934-940.
[152] PROVOST P, DISHART D, DOUCET J, et al. Ribonuclease activity and RNA binding of recombinant human Dicer [J]. The EMBO Journal, 2002, 21(21): 5864-5874.
[153] HOEHENER C, HUG I, NOWACKI M. Dicer-like Enzymes with Sequence Cleavage Preferences [J]. Cell, 2018, 173(1): 234-47 e7.
[154] MATSUDA T, CEPKO C L. Electroporation and RNA interference in the rodent retina in vivo and in vitro [J]. Proceedings of the National Academy of Sciences, 2004, 101(1): 16-22.
[155] MOCHIZUKI K, GOROVSKY M A. A Dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase [J]. Genes & Development, 2005, 19(1): 77-89.
[156] TIAN Y, SIMANSHU D K, MA J B, et al. A Phosphate-Binding Pocket within the Platform-PAZ-Connector Helix Cassette of Human Dicer [J]. Molecular Cell, 2014, 53(4): 606-616.
[157] DENLI A M, TOPS B B, PLASTERK R H, et al. Processing of primary microRNAs by the Microprocessor complex [J]. Nature, 2004, 432(7014): 231-235.
[158] HAN J, LEE Y, YEOM K H, et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex [J]. Cell, 2006, 125(5): 887-901.
[159] WANG T, DENG Z, ZHANG X, et al. Tomato DCL2b is required for the biosynthesis of 22-nt small RNAs, the resulting secondary siRNAs, and the host defense against ToMV [J]. Horticulture Research, 2018, 5: 62.
[160] GAN J, SHAW G, TROPEA J E, et al. A stepwise model for double-stranded RNA processing by ribonuclease III [J]. Molecular Microbiology, 2008, 67(1): 143-154.
[161] JIN W, WANG J, LIU C P, et al. Structural Basis for pri-miRNA Recognition by Drosha [J]. Molecular Cell, 2020, 78(3): 423-433.
[162] LIU Z M, WANG J, CHENG H, et al. Cryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate [J]. Cell, 2018, 173(5): 1191-1203.
[163] DANIELS S M, MELENDEZ-PENA C E, SCARBOROUGH R J, et al. Characterization of the TRBP domain required for dicer interaction and function in RNA interference [J]. BMC Molecular Biology, 2009, 10: 38.
[164] WILSON R C, TAMBE A, KIDWELL M A, et al. Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis [J]. Molecular Cell, 2015, 57(3): 397-407.
[165] GAN J, TROPEA J E, AUSTIN B P, et al. Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III [J]. Cell, 2006, 124(2): 355-366.
[166] MACRAE I J, ZHOU K, DOUDNA J A. Structural determinants of RNA recognition and cleavage by Dicer [J]. Nature Structural & Molecular Biology, 2007, 14(10): 934-940.
[167] LAU P W, POTTER C S, CARRAGHER B, et al. Structure of the human Dicer-TRBP complex by electron microscopy [J]. Structure, 2009, 17(10): 1326-1332.
[168] LAU P W, GUILEY K Z, DE N, et al. The molecular architecture of human Dicer [J]. Nature Structural & Molecular Biology, 2012, 19(4): 436-440.
[169] BLASZCZYK J, TROPEA J E, BUBUNENKO M, et al. Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage [J]. Structure, 2001, 9(12): 1225-1236.
[170] ZAMORE P D. Thirty-three years later, a glimpse at the ribonuclease III active site [J]. Molecular Cell, 2001, 8(6): 1158-1160.
[171] SUN W, PERTZEV A, NICHOLSON A W. Catalytic mechanism of Escherichia coli ribonuclease III: kinetic and inhibitor evidence for the involvement of two magnesium ions in RNA phosphodiester hydrolysis [J]. Nucleic Acids Research, 2005, 33(3): 807-815.
[172] AMARASINGHE A K, CALIN-JAGEMAN I, HARMOUCH A, et al. Escherichia coli ribonuclease III: affinity purification of hexahistidine-tagged enzyme and assays for substrate binding and cleavage [J]. Methods in Enzymology, 2001, 342: 143-158.
[173] CAMPBELL F E, JR., CASSANO A G, ANDERSON V E, et al. Pre-steady-state and stopped-flow fluorescence analysis of Escherichia coli ribonuclease III: insights into mechanism and conformational changes associated with binding and catalysis [J]. Journal of Molecular Biology, 2002, 317(1): 21-40.
[174] LI H L, CHELLADURAI B S, ZHANG K, et al. Ribonuclease III cleavage of a bacteriophage T7 processing signal. Divalent cation specificity, and specific anion effects [J]. Nucleic Acids Research, 1993, 21(8): 1919-1925.
[175] MA J B, YE K, PATEL D J. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain [J]. Nature, 2004, 429(6989): 318-322.
[176] SONG J J, LIU J, TOLIA N H, et al. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes [J]. Nature Structural & Molecular Biology, 2003, 10(12): 1026-1032.
[177] ELKAYAM E, KUHN C D, TOCILJ A, et al. The structure of human argonaute-2 in complex with miR-20a [J]. Cell, 2012, 150(1): 100-110.
[178] MATSUMOTO N, NISHIMASU H, SAKAKIBARA K, et al. Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA [J]. Cell, 2016, 167(2): 484-497.
[179] BAI X C, MCMULLAN G, SCHERES S H. How cryo-EM is revolutionizing structural biology [J]. Trends in Biochemical Sciences, 2015, 40(1): 49-57.
[180] SGRO G G, COSTA T R D. Cryo-EM Grid Preparation of Membrane Protein Samples for Single Particle Analysis [J]. Frontiers in Molecular Biosciences, 2018, 5: 74.
[181] CREGG J M, TOLSTORUKOV I, KUSARI A, et al. Expression in the yeast Pichia pastoris [J]. Methods in Enzymology, 2009, 463: 169-189.
[182] DUROCHER Y, PERRET S, KAMEN A. High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells [J]. Nucleic Acids Research, 2002, 30(2): E9.
[183] UNGER T, PELEG Y. Recombinant protein expression in the baculovirus-infected insect cell system [J]. Methods in Molecular Biology, 2012, 800: 187-199.
[184] RUE S M, ANDERSON P W, GAYLORD M R, et al. A High-Throughput System for Transient and Stable Protein Production in Mammalian Cells [J]. Methods in Molecular Biology, 2019, 2025: 93-142.
[185] BANDARANAYAKE A D, ALMO S C. Recent advances in mammalian protein production [J]. FEBS Letters, 2014, 588(2): 253-260.
[186] BOS A B, LUAN P, DUQUE J N, et al. Optimization and automation of an end-to-end high throughput microscale transient protein production process [J]. Biotechnol Bioeng, 2015, 112(9): 1832-1842.
[187] GEISSE S. Reflections on more than 10 years of TGE approaches [J]. Protein Expression and Purification, 2009, 64(2): 99-107.
[188] SHAW G, MORSE S, ARARAT M, et al. Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells [J]. The FASEB Journal, 2002, 16(8): 869-871.
[189] GRAHAM F L, SMILEY J, RUSSELL W C, et al. Characteristics of a human cell line transformed by DNA from human adenovirus type 5 [J]. Journal of General Virology, 1977, 36(1): 59-74.
[190] SUEN K F, TURNER M S, GAO F, et al. Transient expression of an IL-23R extracellular domain Fc fusion protein in CHO vs. HEK cells results in improved plasma exposure [J]. Protein Expression and Purification, 2010, 71(1): 96-102.
[191] CROSET A, DELAFOSSE L, GAUDRY J P, et al. Differences in the glycosylation of recombinant proteins expressed in HEK and CHO cells [J]. Journal of Biotechnology, 2012, 161(3): 336-348.
[192] KIM J Y, KIM Y G, LEE G M. CHO cells in biotechnology for production of recombinant proteins: current state and further potential [J]. Applied Microbiology and Biotechnology, 2012, 93(3): 917-930.
[193] LONGO P A, KAVRAN J M, KIM M S, et al. Transient mammalian cell transfection with polyethylenimine (PEI) [J]. Methods in Enzymology, 2013, 529: 227-240.
[194] LAURENTI D, OOI L. Mammalian expression systems and transfection techniques [J]. Methods in Molecular Biology, 2013, 998: 21-32.
[195] BOUSSIF O, LEZOUALC'H F, ZANTA M A, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine [J]. proceedings of the national academy of sciences, 1995, 92(16): 7297-7301.
[196] HAO F, LI Y, ZHU J, et al. Polyethylenimine-based Formulations for Delivery of Oligonucleotides [J]. Current Medicinal Chemistry, 2019, 26(13): 2264-2284.
[197] SONAWANE N D, SZOKA F C, JR., VERKMAN A S. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes [J]. Journal of Biological Chemistry, 2003, 278(45): 44826-44831.
[198] PARIS S, BURLACU A, DUROCHER Y. Opposing roles of syndecan-1 and syndecan-2 in polyethyleneimine-mediated gene delivery [J]. Journal of Biological Chemistry, 2008, 283(12): 7697-7704.
[199] PAYNE C K, JONES S A, CHEN C, et al. Internalization and trafficking of cell surface proteoglycans and proteoglycan-binding ligands [J]. Traffic, 2007, 8(4): 389-401.
[200] KOPATZ I, REMY J S, BEHR J P. A model for non-viral gene delivery: through syndecan adhesion molecules and powered by actin [J]. The Journal of Gene Medicine, 2004, 6(7): 769-776.
[201] ZHAO Y, BISHOP B, CLAY J E, et al. Automation of large scale transient protein expression in mammalian cells [J]. Journal of Structural Biology, 2011, 175(2): 209-215.
[202] POSSEE R D. Baculoviruses as expression vectors [J]. Current Opinion in Biotechnology, 1997, 8(5): 569-572.
[203] MILLER L K. Baculoviruses as Gene-Expression Vectors [J]. Annual Review of Microbiology, 1988, 42: 177-199.
[204] KIDD I M, EMERY V C. The Use of Baculoviruses as Expression Vectors [J]. Applied Biochemistry and Biotechnology, 1993, 42(2-3): 137-159.
[205] ATKINSON A E, WEITZMAN M D, OBOSI L, et al. Baculoviruses as Vectors for Foreign Gene-Expression in Insect Cells [J]. pesticide science, 1990, 28(2): 215-224.
[206] FRASER M J. Ultrastructural Observations of Virion Maturation in Autographa-Californica Nuclear Polyhedrosis-Virus Infected Spodoptera-Frugiperda Cell-Cultures [J]. Journal of Molecular Structure, 1986, 95(1-3): 189-195.
[207] SHANG H, GARRETSON T A, KUMAR C M S, et al. Improved pFastBac (TM) donor plasmid vectors for higher protein production using the Bac-to-Bac (R) baculovirus expression vector system [J]. Journal of Biotechnology, 2017, 255: 37-46.
[208] VAUGHN J L, GOODWIN R H, TOMPKINS G J, et al. The establishment of two cell lines from the insect Spodoptera frugiperda (Lepidoptera; Noctuidae) [J]. In Vitro, 1977, 13(4): 213-217.
[209] JARVIS D L. Baculovirus-insect cell expression systems [J]. Methods in Enzymology, 2009, 463: 191-222.
[210] LUCKOW V A, LEE S C, BARRY G F, et al. Efficient Generation of Infectious Recombinant Baculoviruses by Site-Specific Transposon-Mediated Insertion of Foreign Genes into a Baculovirus Genome Propagated in Escherichia-Coli [J]. Journal of Virology, 1993, 67(8): 4566-4579.
[211] VIALARD J E, RICHARDSON C D. The 1,629-nucleotide open reading frame located downstream of the Autographa californica nuclear polyhedrosis virus polyhedrin gene encodes a nucleocapsid-associated phosphoprotein [J]. JOURNAL OF VIROLOGY, 1993, 67(10): 5859-5866.
[212] ADENIYI A A, LUA L H. Protein Expression in the Baculovirus-Insect Cell Expression System [J]. Methods in Molecular Biology, 2020, 2073: 17-37.
[213] SARI D, GUPTA K, THIMIRI GOVINDA RAJ D B, et al. The MultiBac Baculovirus/Insect Cell Expression Vector System for Producing Complex Protein Biologics [J]. Advances in Experimental Medicine and Biology, 2016, 896: 199-215.
[214] JENSEN I S, INUI K, DRAKULIC S, et al. Expression of Flp Protein in a Baculovirus/Insect Cell System for Biotechnological Applications [J]. The Protein Journal, 2017, 36(4): 332-342.
[215] MASOOMI DEZFOOLI S, TAN W S, TEY B T, et al. Expression and purification of the matrix protein of Nipah virus in baculovirus insect cell system [J]. Biotechnology Progress, 2016, 32(1): 171-177.
[216] MAHAJAN P, STRAIN-DAMERELL C, GILEADI O, et al. Medium-throughput production of recombinant human proteins: protein production in insect cells [J]. Methods in Molecular Biology, 2014, 1091: 95-121.
[217] SHI Y G. A Glimpse of Structural Biology through X-Ray Crystallography [J]. Cell, 2014, 159(5): 995-1014.
[218] WATSON J D, CRICK F H. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid [J]. Nature, 1953, 171(4356): 737-738.
[219] KENDREW J C, BODO G, DINTZIS H M, et al. A three-dimensional model of the myoglobin molecule obtained by x-ray analysis [J]. Nature, 1958, 181(4610): 662-666.
[220] KENDREW J C, DICKERSON R E, STRANDBERG B E, et al. Structure of myoglobin: A three-dimensional Fourier synthesis at 2 A. resolution [J]. Nature, 1960, 185(4711): 422-427.
[221] BAX A, CLORE G M. Protein NMR: Boundless opportunities [J]. Journal of Magnetic Resonance, 2019, 306: 187-191.
[222] RANKIN N J, PREISS D, WELSH P, et al. The emergence of proton nuclear magnetic resonance metabolomics in the cardiovascular arena as viewed from a clinical perspective [J]. Atherosclerosis, 2014, 237(1): 287-300.
[223] EARL L A, FALCONIERI V, MILNE J L, et al. Cryo-EM: beyond the microscope [J]. Current Opinion in Structural Biology, 2017, 46: 71-78.
[224] CHENG Y F. Single-particle cryo-EM-How did it get here and where will it go [J]. Science, 2018, 361(6405): 876-880.
[225] NOGALES E. The development of cryo-EM into a mainstream structural biology technique [J]. Nature Methods, 2016, 13(1): 24-27.
[226] CALLAWAY E. The revolution will not be crystallized: a new method sweeps through structural biology [J]. Nature, 2015, 525(7568): 172-174.
[227] FRANK J. Averaging of low exposure electron micrographs of non-periodic objects [J]. Ultramicroscopy, 1975, 1(2): 159-162.
[228] DEROSIER D J, KLUG A. Structure of the tubular variants of the head of bacteriophage T4 (polyheads). I. Arrangement of subunits in some classes of polyheads [J]. Journal of Molecular Biology, 1972, 65(3): 469-488.
[229] BAKER L A, RUBINSTEIN J L. Radiation damage in electron cryomicroscopy [J]. Methods in Enzymology, 2010, 481: 371-388.
[230] DANEV R, YANAGISAWA H, KIKKAWA M. Cryo-Electron Microscopy Methodology: Current Aspects and Future Directions [J]. Trends in Biochemical Sciences, 2019, 44(10): 837-848.
[231] FRANK J. Single-particle imaging of macromolecules by cryo-electron microscopy [J]. Annual Review of Biophysics and Biomolecular Structure, 2002, 31: 303-319.
[232] DE ROSIER D J, KLUG A. Reconstruction of three dimensional structures from electron micrographs [J]. Nature, 1968, 217(5124): 130-134.
[233] FRANK J. Single-Particle Reconstruction of Biological Molecules-Story in a Sample (Nobel Lecture) [J]. Angewandte Chemie - International Edition, 2018, 57(34): 10826-10841.
[234] CHENG Y, GRIGORIEFF N, PENCZEK P A, et al. A primer to single-particle cryo-electron microscopy [J]. Cell, 2015, 161(3): 438-449.
[235] ZHOU J, CHIZHIK A I, CHU S, et al. Single-particle spectroscopy for functional nanomaterials [J]. Nature, 2020, 579(7797): 41-50.
[236] SKINIOTIS G, SOUTHWORTH D R. Single-particle cryo-electron microscopy of macromolecular complexes [J]. Microscopy , 2016, 65(1): 9-22.
[237] THOMPSON R F, WALKER M, SIEBERT C A, et al. An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology [J]. Methods, 2016, 100: 3-15.
[238] PASSMORE L A, RUSSO C J. Specimen Preparation for High-Resolution Cryo-EM [J]. Methods in Enzymology, 2016, 579: 51-86.
[239] GALLAGHER J R, KIM A J, GULATI N M, et al. Negative-Stain Transmission Electron Microscopy of Molecular Complexes for Image Analysis by 2D Class Averaging [J]. Current Protocols in Microbiology, 2019, 54(1): e90.
[240] KISELEV N A, SHERMAN M B, TSUPRUN V L. Negative staining of proteins [J]. Electron Microscopy Reviews, 1990, 3(1): 43-72.
[241] OHI M, LI Y, CHENG Y, et al. Negative Staining and Image Classification - Powerful Tools in Modern Electron Microscopy [J]. Biological Procedures Online, 2004, 6: 23-34.
[242] BRENNER S, HORNE R W. A negative staining method for high resolution electron microscopy of viruses [J]. Biochimica et Biophysica Acta, 1959, 34: 103-110.
[243] FRANK J, GOLDFARB W, EISENBERG D, et al. Reconstruction of glutamine synthetase using computer averaging [J]. Ultramicroscopy, 1978, 3(3): 283-290.
[244] SCARFF C A, FULLER M J G, THOMPSON R F, et al. Variations on Negative Stain Electron Microscopy Methods: Tools for Tackling Challenging Systems [J]. Jove-Journal of Visualized Experiments, 2018, (132): 57199.
[245] BRILLAULT L, LANDSBERG M J. Preparation of Proteins and Macromolecular Assemblies for Cryo-electron Microscopy [J]. Methods in Molecular Biology, 2020, 2073: 221-246.
[246] HENDERSON R. The potential and limitations of neutrons, electrons and X-rays for atomic resolution microscopy of unstained biological molecules [J]. Quarterly Reviews of Biophysics, 1995, 28(2): 171-193.
[247] GLAESER R M. Limitations to significant information in biological electron microscopy as a result of radiation damage [J]. Journal of Ultrastructure Research, 1971, 36(3): 466-482.
[248] GLAESER R M. Prospects for extending the resolution limit of the electron microscope [J]. Journal of Microscopy, 1979, 117(1): 77-91.
[249] ADRIAN M, DUBOCHET J, LEPAULT J, et al. Cryo-electron microscopy of viruses [J]. Nature, 1984, 308(5954): 32-36.
[250] DUBOCHET J, CHANG J J, FREEMAN R, et al. Frozen Aqueous Suspensions [J]. Ultramicroscopy, 1982, 10(1-2): 55-61.
[251] TAYLOR K A, GLAESER R M. Electron diffraction of frozen, hydrated protein crystals [J]. Science, 1974, 186(4168): 1036-1037.
[252] BAMMES B E, JAKANA J, SCHMID M F, et al. Radiation damage effects at four specimen temperatures from 4 to 100 K [J]. Journal of Structural Biology, 2010, 169(3): 331-341.
[253] HENDERSON R. Cryoprotection of Protein Crystals against Radiation-Damage in Electron and X-Ray-Diffraction [J]. Proceedings of The Royal Society B-Biological Sciences, 1990, 241(1300): 6-8.
[254] WEISSENBERGER G, HENDERIKX R J M, PETERS P J. Understanding the invisible hands of sample preparation for cryo-EM [J]. Nature Methods, 2021, 18(5): 463-471.
[255] RHEINBERGER J, OOSTERGETEL G, RESCH G P, et al. Optimized cryo-EM data-acquisition workflow by sample-thickness determination [J]. Acta Crystallographica Section D: Structural Biology, 2021, 77(Pt 5): 565-571.
[256] MOONEY P. Optimization of image collection for cellular electron microscopy [J]. Methods in Cell Biology, 2007, 79: 661-719.
[257] SULOWAY C, PULOKAS J, FELLMANN D, et al. Automated molecular microscopy: the new Leginon system [J]. Journal of Structural Biology, 2005, 151(1): 41-60.
[258] LIAO M, CAO E, JULIUS D, et al. Structure of the TRPV1 ion channel determined by electron cryo-microscopy [J]. Nature, 2013, 504(7478): 107-112.
[259] MCMULLAN G, FARUQI A R, HENDERSON R. Direct Electron Detectors [J]. Methods in Enzymology, 2016, 579: 1-17.
[260] BRILOT A F, CHEN J Z, CHENG A, et al. Beam-induced motion of vitrified specimen on holey carbon film [J]. Journal of Structural Biology, 2012, 177(3): 630-637.
[261] SCHERES S H. RELION: implementation of a Bayesian approach to cryo-EM structure determination [J]. Journal of Structural Biology, 2012, 180(3): 519-530.
[262] SCHERES S H. A Bayesian view on cryo-EM structure determination [J]. Journal of Molecular Biology, 2012, 415(2): 406-418.
[263] SCAPIN G, PROSISE W W, WISMER M K, et al. A novel storage system for cryoEM samples [J]. Journal of Structural Biology, 2017, 199(1): 84-86.
[264] SCHERES S H W. Amyloid structure determination in RELION-3.1 [J]. Acta Crystallographica Section D: Structural Biology, 2020, 76(Pt 2): 94-101.
[265] ZIVANOV J, NAKANE T, FORSBERG B O, et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3 [J]. Elife, 2018, 7: e42166.
[266] ZHENG S Q, PALOVCAK E, ARMACHE J P, et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy [J]. Nature Methods, 2017, 14(4): 331-332.
[267] ROHOU A, GRIGORIEFF N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs [J]. Journal of Structural Biology, 2015, 192(2): 216-221.
[268] SU M. goCTF: Geometrically optimized CTF determination for single-particle cryo-EM [J]. Journal of Structural Biology, 2019, 205(1): 22-29.
[269] EMSLEY P, LOHKAMP B, SCOTT W G, et al. Features and development of Coot [J]. Acta Crystallographica Section D: Biological Crystallography, 2010, 66(Pt 4): 486-501.
[270] AFONINE P V, POON B K, READ R J, et al. Real-space refinement in PHENIX for cryo-EM and crystallography [J]. Acta Crystallographica Section D: Structural Biology, 2018, 74(Pt 6): 531-544.
[271] ADAMS P D, AFONINE P V, BUNKOCZI G, et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution [J]. Acta Crystallographica Section D: Biological Crystallography, 2010, 66(Pt 2): 213-221.
[272] PETTERSEN E F, GODDARD T D, HUANG C C, et al. UCSF Chimera--a visualization system for exploratory research and analysis [J]. Journal of Computational Chemistry, 2004, 25(13): 1605-1612.
[273] LIN B, MENG H, BING H, et al. Efficient expression of acetylcholine-binding protein from Aplysia californica in Bac-to-Bac system [J]. BioMed Research International, 2014, 2014: 691480.
[274] RAMACHANDRAN V, CHEN X. Degradation of microRNAs by a family of exoribonucleases in Arabidopsis [J]. Science, 2008, 321(5895): 1490-1492.
[275] LI J, YANG Z, YU B, et al. Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis [J]. Current Biology, 2005, 15(16): 1501-1507.
[276] HUANG R H. Unique 2'-O-methylation by Hen1 in eukaryotic RNA interference and bacterial RNA repair [J]. Biochemistry, 2012, 51(20): 4087-4095.
[277] HUANG Y, JI L J, HUANG Q C, et al. Structural insights into mechanisms of the small RNA methyltransferase HEN1 [J]. Nature, 2009, 461(7265): 823-827.
[278] YU B, YANG Z Y, LI J J, et al. Methylation as a crucial step in plant microRNA biogenesis [J]. Science, 2005, 307(5711): 932-935.
[279] YANG Z Y, EBRIGHT Y W, YU B, et al. HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2 ' OH of the 3 ' terminal nucleotide [J]. Nucleic Acids Research, 2006, 34(2): 667-675.
[280] ABOU ELELA S, JI X. Structure and function of Rnt1p: An alternative to RNAi for targeted RNA degradation [J]. Wiley Interdisciplinary Reviews-RNA, 2019, 10(3): e1521.
[281] SONG H, FANG X, JIN L, et al. The Functional Cycle of Rnt1p: Five Consecutive Steps of Double-Stranded RNA Processing by a Eukaryotic RNase III [J]. Structure, 2017, 25(2): 353-363.

Academic Degree Assessment Sub committee
生物系
Domestic book classification number
Q945.78
Data Source
人工提交
Document TypeThesis
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/343014
DepartmentDepartment of Biology
Recommended Citation
GB/T 7714
王倩. 拟南芥 Dicer 家族蛋白 DCL3 的结构功能研究[D]. 深圳. 南方科技大学,2022.
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