TbTRF suppresses the TERRA level and regulates the cell cycle-dependent TERRA foci number with a TERRA binding activity in its C-terminal Myb domain.
TbTRF suppresses the TERRA level and regulates the cell cycle-dependent TERRA foci number with a TERRA binding activity in its C-terminal Myb domain.
复制标题
DOI：
10.1093/nar/gkab401
复制
发表时间：
2021-06-04
影响因子：
14.9
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Saha A;Gaurav AK;Pandya UM;Afrin M;Sandhu R;Nanavaty V;Schnur B;Li B
端粒重复序列RNA （TERRA）已在多种生物中被发现，包括布鲁氏锥虫（一种引起非洲人类锥虫病的原生动物寄生虫）。布鲁氏杆菌经常改变其主要表面抗原VSG，以逃避宿主的免疫反应。VSG完全从亚端粒表达位点表达，我们已经证明端粒蛋白在VSG沉默和开关的调控中起重要作用。在这项研究中，我们发现了一些独特的TERRA和端粒生物学特征。首先，TERRA灶的数量受布鲁氏体双端粒DNA结合因子TbTRF的细胞周期调控和影响。其次，TERRA主要由活性VSG下游的单个端粒的RNA聚合酶I转录。第三，TbTRF通过同样具有双链DNA结合活性的c端Myb结构域以序列特异性方式结合TERRA，抑制TERRA水平而不影响其半衰期。最后，端粒r环和端粒DNA损伤水平在ttrf耗尽后增加。在TbTRF RNAi细胞中，RNase H1的异位等位基因过表达可以部分抑制这些表型，揭示了TbTRF如何帮助维持端粒完整性的潜在机制。
Telomere repeat-containing RNA (TERRA) has been identified in multiple organisms including Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis. T. brucei regularly switches its major surface antigen, VSG, to evade the host immune response. VSG is expressed exclusively from subtelomeric expression sites, and we have shown that telomere proteins play important roles in the regulation of VSG silencing and switching. In this study, we identify several unique features of TERRA and telomere biology in T. brucei. First, the number of TERRA foci is cell cycle-regulated and influenced by TbTRF, the duplex telomere DNA binding factor in T. brucei. Second, TERRA is transcribed by RNA polymerase I mainly from a single telomere downstream of the active VSG. Third, TbTRF binds TERRA through its C-terminal Myb domain, which also has the duplex DNA binding activity, in a sequence-specific manner and suppresses the TERRA level without affecting its half-life. Finally, levels of the telomeric R-loop and telomere DNA damage were increased upon TbTRF depletion. Overexpression of an ectopic allele of RNase H1 that resolves the R-loop structure in TbTRF RNAi cells can partially suppress these phenotypes, revealing an underlying mechanism of how TbTRF helps maintain telomere integrity.
登录
查看更多内容
影响因子：
14.9
作者：
Bah A;Wischnewski H;Shchepachev V;Azzalin CM
通讯作者：
Azzalin CM
影响因子：
56.9
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
通讯作者：
Lingner, Joachim
影响因子：
5.3
作者：
Cestari, Igor;McLeland-Wieser, Hilary;Stuart, Kenneth
通讯作者：
Stuart, Kenneth
影响因子：
7.7
作者：
Devlin, Rebecca;Marques, Catarina A.;McCulloch, Richard
通讯作者：
McCulloch, Richard
影响因子：
11.4
作者：
CHUNG, HMM;SHEA, C;VANDERPLOEG, LHT
通讯作者：
VANDERPLOEG, LHT