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题名

The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression

作者
通讯作者Zhao,Yanxiang; Li,Bibo
发表日期
2023-03-22
DOI
发表期刊
EISSN
2041-1723
卷号14期号:1
摘要

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.

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英语
重要成果
NI论文
学校署名
其他
资助项目
National Institute of Allergy and Infectious Diseases[AI066095] ; NIH Office of the Director[S10OD025252]
WOS研究方向
Science & Technology - Other Topics
WOS类目
Multidisciplinary Sciences
WOS记录号
WOS:001063479500019
出版者
Scopus记录号
2-s2.0-85150849558
来源库
Scopus
引用统计
被引频次[WOS]:5
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/524080
专题生命科学学院
作者单位
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
推荐引用方式
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).
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).
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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