2026-06-14T03:30:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/172012024-11-29T17:18:05Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Gaurav, Amit Kumar
author
Afrin, Marjia
author
Yang, Xian
author
Sayeed, S K Abdus
author
Pan, Xuehua
author
Ji, Zeyang
author
Wong, Kam-Bo
author
Zhang, Mingjie
author
Zhao, Yanxiang
author
Li, Bibo
funder
NIH - National Cancer Institute (NCI) (Estados Unidos)
funder
Hong Kong Research Grants Council
2024-01-17T12:21:06Z
2024-01-17T12:21:06Z
2023-03-22
Nat Commun . 2023 ;14(1):1576.
10.1038/s41467-023-37307-0
2041-1723
Nature communications
36949076
http://hdl.handle.net/20.500.12105/17201
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 737RKRRR741 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 737RKRRR741 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.
eng
The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression.
journal article
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