RTEL1 influences the abundance and localization of TERRA RNA.
RTEL1 influences the abundance and localization of TERRA RNA.
复制标题
RTEL1影响TERRA RNA的丰度和定位。
DOI：
10.1038/s41467-021-23299-2
复制
发表时间：
2021-05-21
影响因子：
16.6
通讯作者：
Petrini JHJ
中科院分区：
文献类型：
--
作者：
Ghisays F;Garzia A;Wang H;Canasto-Chibuque C;Hohl M;Savage SA;Tuschl T;Petrini JHJ
端粒重复序列RNA（Telomere repeat containing RNA，TERRA）是一类由真核生物染色体端粒下区域转录的非编码长链RNA。TERRA转录本可以在染色体末端形成R环;然而，这些结构的重要性或TERRA表达的调节和端粒R环中的保留仍然不清楚。在这里，我们表明，RTEL 1（端粒长度调节1）解旋酶影响人类细胞中TERRA的丰度和定位。RTEL 1的缺失导致TERRA RNA水平的增加，同时减少端粒处含有TERRA的R环。在体外，RTEL 1表现出强烈的偏好结合G-四链体结构，形成TERRA。这种结合是由RTEL 1的C-末端区域介导的，并且不依赖于RTEL 1解旋酶结构域。与TERRA结合的RTEL 1似乎对细胞活力至关重要，强调了这一功能的重要性。通过过度表达RNA酶H1降解含TERRA的R环部分地再现了与RTEL 1缺陷相关的TERRA水平增加和端粒不稳定性。总的来说，这些数据表明，TERRA的调节是RTEL 1解旋酶的关键功能，该功能的丧失可能导致RTEL 1突变患者的疾病表型。长的非编码RNA TERRA转录物可以在染色体末端形成R环。在这里，作者揭示了解旋酶RTEL在影响TERRA水平和定位中的作用。
Telomere repeat containing RNAs (TERRAs) are a family of long non-coding RNAs transcribed from the subtelomeric regions of eukaryotic chromosomes. TERRA transcripts can form R-loops at chromosome ends; however the importance of these structures or the regulation of TERRA expression and retention in telomeric R-loops remain unclear. Here, we show that the RTEL1 (Regulator of Telomere Length 1) helicase influences the abundance and localization of TERRA in human cells. Depletion of RTEL1 leads to increased levels of TERRA RNA while reducing TERRA-containing R loops at telomeres. In vitro, RTEL1 shows a strong preference for binding G-quadruplex structures which form in TERRA. This binding is mediated by the C-terminal region of RTEL1, and is independent of the RTEL1 helicase domain. RTEL1 binding to TERRA appears to be essential for cell viability, underscoring the importance of this function. Degradation of TERRA-containing R-loops by overexpression of RNAse H1 partially recapitulates the increased TERRA levels and telomeric instability associated with RTEL1 deficiency. Collectively, these data suggest that regulation of TERRA is a key function of the RTEL1 helicase, and that loss of that function may contribute to the disease phenotypes of patients with RTEL1 mutations. Long non coding RNA TERRA transcripts can form R-loops at chromosome ends. Here, the authors reveal a role for the helicase RTEL in affecting TERRA levels and localization.
登录
查看更多内容
影响因子：
4.5
作者：
Ballew BJ;Joseph V;De S;Sarek G;Vannier JB;Stracker T;Schrader KA;Small TN;O'Reilly R;Manschreck C;Harlan Fleischut MM;Zhang L;Sullivan J;Stratton K;Yeager M;Jacobs K;Giri N;Alter BP;Boland J;Burdett L;Offit K;Boulton SJ;Savage SA;Petrini JH
通讯作者：
Petrini JH
影响因子：
16.6
作者：
Arora, Rajika;Lee, Yongwoo;Wischnewski, Harry;Brun, Catherine M.;Schwarz, Tobias;Azzalin, Claus M.
通讯作者：
Azzalin, Claus M.
影响因子：
16.6
作者：
Garzia, Aitor;Jafarnejad, Seyed Mehdi;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
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：
16.6
作者：
Beishline K;Vladimirova O;Tutton S;Wang Z;Deng Z;Lieberman PM
通讯作者：
Lieberman PM