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

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 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 activ

SUBMITTER: Gaurav AK 

PROVIDER: S-EPMC10033678 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature