2026-06-14T03:31:57Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/172012024-11-29T17:18:05Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2023-03-22 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. 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 The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression.