Poster abstracts
Poster number 144 submitted by Amit Gaurav
Trypanosoma brucei TTAGGG repeat binding factor interacts with TERRA independent to its DNA binding activity.
Amit Kumar Gaurav (GRHD, BGES, Cleveland State University), Vishal Nanavaty (Genomic Medicine Institute, Cleveland Clinic), Ranjodh Sandhu (Department of Microbiology and Molecular Genetics, University of California, Davis), Unnati Pandya (Vincent Center for Reproductive Biology, Massachusetts General Hospital), Bibo Li (GRHD, BGES, Cleveland State University)
Abstract:
Protozoan parasite Trypanosoma brucei causes African sleeping sickness in humans and Nagana in cattle. T. brucei evades the host immune response by regularly switching its major surface antigen, Variant Surface Glycoprotein (VSG). VSGs are exclusively expressed from sub-telomeric expression sites in a monoallelic manner. We have previously shown that telomere proteins play essential roles in the regulation of VSG switching and silencing. We identified telomeric proteins TbTRF, a TTAGGG repeat binding factor and TbRAP1. We have shown that TbRAP1 is essential for VSG silencing and it suppresses VSG switching. We have also shown that TbTRF is essential for protection of telomeric G-overhang structure and suppression of VSG switching. Recently we showed that the T. brucei telomere is transcribed into a long non-coding RNA called TElomeric Repeats-containing RNA (TERRA). It appears that higher levels of TERRA is linked to more telomeric RNA-DNA hybrids, which causes increased sub-telomeric DNA double strand breaks and more frequent VSG switching. Now we show that TbTRF associates with G-rich TERRA in vivo. Additionally, TbTRF depletion leads to higher TERRA levels. With electrophoretic mobility shift assays, we demonstrate that TbTRF binds directly to G-strand TERRA in vitro and its RNA binding activity is independent of its double-stranded telomere DNA binding activity. These results suggest a possible mechanism of TbTRF regulated VSG switching and telomere stability maintenance through TERRA interaction.
Keywords: TERRA, Telomere, Trypanosoma brucei