Abstract: Telomeres are nucleoprotein complexes located at chromosome ends and are essential for genome integrity and chromosome stability. In many organisms including T. brucei, telomeres form a heterochromatic structure and suppress the expression of nearby genes, which is termed telomere position effect. T. brucei’s major surface antigen, VSG, is exclusively expressed from one of multiple VSG expression sites located immediately upstream of the telomere. Previously, we have shown that TbRAP1, a telomere protein, plays crucial roles in VSG regulation. In TbRAP1-depleted cells, nearly all subtelomeric VSGs were derepressed. TbRAP1 also suppresses telomeric transcript (TERRA) and telomeric R-loop levels. All these TbRAP1 functions rely on its association with the telomere chromatin. We have shown that TbRAP1, unlike its homologues in yeast or vertebrates, has unique DNA binding activities that are required for its telomere association. However, it is still unknown how does TbRAP1 allows the active VSG to be fully expressed at a high level while silencing all other telomeric VSG genes. We now have discovered that TbRAP1 has an RNA binding activity. Furthermore, structural analysis reveals an RRM motif in the TbRAP1 MybLike domain, which is novel among all known RAP1 homologues. 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.

Meeting ID: 935 4749 4786
Passcode: 623256