m6A-modified lincRNA Dubr is required for neuronal development by stabilizing YTHDF1/3 and facilitating mRNA translation

Huang，Jiansong1; Jiang，Bowen1; Li，Guo Wei3; Zheng，Dandan4; Li，Mingyi1; Xie，Xuan1; Pan，Yuxiang1; Wei，Manyi1; Liu，Xiaoyan6; Jiang，Xingyu6; Zhang，Xu2,5,7; Yang，Li8; Bao，Lan1,4; Wang，Bin1,2

2022-11-22

10.1016/j.celrep.2022.111693

Cell Reports   Impact Factor & Quartile

2211-1247

2211-1247

Long intergenic noncoding RNAs (lincRNAs) are crucial regulators in numerous biological processes. However, the functions and mechanisms of mA-modified lincRNAs in neuronal development remain unclear. Here, we report an mA-modified lincRNA, Dppa2 upstream binding RNA (Dubr), abundantly expressed at the early developmental stage of dorsal root ganglion (DRG) and cerebral cortex. Silencing Dubr impairs axon elongation of DRG neurons and axon projection and migration of cortical neurons, whereas lacking mA modification of Dubr fully loses its functions. Mechanically, Dubr interacts with mA-binding proteins, the YTHDF1/3 complex, through its mA motifs to protect YTHDF1/3 from degradation via the proteasome pathway. Furthermore, Tau and Calmodulin are regulated by YTHDF1/3 and mA-modified Dubr. Overexpression of YTHDF1/3 not only rescues the reduced Tau and Calmodulin but also restores axon elongation of DRG neurons by Dubr knockdown. This study uncovers a critical role of mA-modified lincRNA in neuronal development by regulating the degradation of RNA-binding protein.

CP: Molecular biology CP: Neuroscience Dubr m6A-modified lincRNA mRNA translation Neuronal development YTHDF1 YTHDF3

SCI

English

Others

National Natural Science Foundation of China[32070967];National Natural Science Foundation of China[32070968];

Cell Biology

Cell Biology

WOS:000892121000006

CELL PRESS

2-s2.0-85142141286

Scopus

1.State Key Laboratory of Cell Biology,Shanghai Institute of Biochemistry and Cell Biology,CAS Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai,200031,China
2.Guangdong Institute of Intelligence Science and Technology,Zhuhai,Hengqin,519031,China
3.CAS Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,Shanghai,200031,China
4.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China
5.Institute of Neuroscience and State Key Laboratory of Neuroscience,CAS Center for Excellence in Brain Science and Intelligence Technology,Shanghai,200031,China
6.Southern University of Science and Technology,Shenzhen,518055,China
7.Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai,201210,China
8.Center for Molecular Medicine,Children's Hospital,Fudan University and Shanghai Key Laboratory of Medical Epigenetics,International Laboratory of Medical Epigenetics and Metabolism,Ministry of Science and Technology,Institutes of Biomedical Sciences,Fudan University,Shanghai,200031,China

Huang，Jiansong,Jiang，Bowen,Li，Guo Wei,et al. m6A-modified lincRNA Dubr is required for neuronal development by stabilizing YTHDF1/3 and facilitating mRNA translation[J]. Cell Reports,2022,41(8).

Huang，Jiansong.,Jiang，Bowen.,Li，Guo Wei.,Zheng，Dandan.,Li，Mingyi.,...&Wang，Bin.(2022).m6A-modified lincRNA Dubr is required for neuronal development by stabilizing YTHDF1/3 and facilitating mRNA translation.Cell Reports,41(8).

Huang，Jiansong,et al."m6A-modified lincRNA Dubr is required for neuronal development by stabilizing YTHDF1/3 and facilitating mRNA translation".Cell Reports 41.8(2022).