| Title | The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression |
| Author | |
| Corresponding Author | Zhao，Yanxiang; Li，Bibo |
| Publication Years | 2023-03-22
|
| DOI | |
| Source Title | |
| EISSN | 2041-1723
|
| Volume | 14Issue:1 |
| Abstract | Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. Its major surface antigen VSG is expressed from subtelomeric loci in a strictly monoallelic manner. We previously showed that the telomere protein TbRAP1 binds dsDNA through its RKRRR patch to silence VSGs globally. How TbRAP1 permits expression of the single active VSG is unknown. Through NMR structural analysis, we unexpectedly identify an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. Assisted by the RKRRR patch, TbRAP1 RRM recognizes consensus sequences of VSG 3’UTRs in vitro and binds the active VSG RNA in vivo. Mutating conserved RRM residues abolishes the RNA binding activity, significantly decreases the active VSG RNA level, and derepresses silent VSGs. The competition between TbRAP1’s RNA and dsDNA binding activities suggests a VSG monoallelic expression mechanism in which the active VSG’s abundant RNA antagonizes TbRAP1’s silencing effect, thereby sustaining its full-level expression. |
| URL | [Source Record] |
| Indexed By | |
| Language | English
|
| Important Publications | NI Journal Papers
|
| SUSTech Authorship | Others
|
| Funding Project | National Institute of Allergy and Infectious Diseases[AI066095]
; NIH Office of the Director[S10OD025252]
|
| Scopus EID | 2-s2.0-85150849558
|
| Data Source | Scopus
|
| Citation statistics |
Cited Times [WOS]:0
|
| Document Type | Journal Article |
| Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/524080 |
| Department | School of Life Sciences |
| Affiliation | 1.Center for Gene Regulation in Health and Disease,Department of Biological,Geological,and Environmental Sciences,College of Arts and Sciences,Cleveland State University,Cleveland,2121 Euclid Avenue,44115,United States 2.Department of Applied Biology and Chemical Technology,State Key Laboratory of Chemical Biology and Drug Discovery,The Hong Kong Polytechnic University,Hung Hom,Kowloon,Hong Kong 3.The Hong Kong Polytechnic University Shenzhen Research Institute,Shenzhen,518057,China 4.Division of Life Science,Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong 5.Centre for Protein Science and Crystallography,School of Life Sciences,State Key Laboratory of Agrobiotechnology,The Chinese University of Hong Kong (CUHK),Shatin,Hong Kong 6.School of Life Sciences,Southern University of Science and Technology,Shenzhen,518055,China 7.Case Comprehensive Cancer Center,Case Western Reserve University,Cleveland,10900 Euclid Avenue,44106,United States 8.Department of Inflammation and Immunity,Lerner Research Institute,Cleveland Clinic,9500 Euclid Avenue,Cleveland,44195,United States 9.Center for RNA Science and Therapeutics,Case Western Reserve University,Cleveland,10900 Euclid Avenue,44106,United States 10.The Wistar Institute,Philadelphia,19104,United States 11.Institute for Stem cell Biology and Regenerative Medicine,Stanford School of medicine,Stanford University,Palo Alto,94305,United States 12.Telomeres and Telomerase Group,Molecular Oncology Program,Spanish National Cancer Centre (CNIO),Madrid,28029,Spain |
| Recommended Citation GB/T 7714 |
Gaurav，Amit Kumar,Afrin，Marjia,Yang，Xian,et al. The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression[J]. Nature Communications,2023,14(1).
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| APA |
Gaurav，Amit Kumar.,Afrin，Marjia.,Yang，Xian.,Saha，Arpita.,Sayeed，S. K.Abdus.,...&Li，Bibo.(2023).The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression.Nature Communications,14(1).
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| MLA |
Gaurav，Amit Kumar,et al."The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression".Nature Communications 14.1(2023).
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