ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells.
ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells.
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ADAR1 RNA编辑酶调节癌细胞端粒r环形成和基因组稳定性。
DOI：
10.1038/s41467-021-21921-x
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发表时间：
2021-03-12
影响因子：
16.6
通讯作者：
Nishikura K
中科院分区：
文献类型：
--
作者：
Shiromoto Y;Sakurai M;Minakuchi M;Ariyoshi K;Nishikura K
ADAR 1参与腺苷到肌苷RNA编辑。细胞质ADAR1p150编辑3'UTR双链RNA，从而抑制干扰素的诱导。这种ADAR1p150功能的丧失是Adar1基因敲除小鼠的胚胎致死性、严重自身免疫性疾病Aicardi-Goutières综合征的发病机制以及癌症对免疫检查点阻断的抗性的基础。相反，核定位的ADAR1p110的生物学功能在很大程度上仍然未知。在这里，我们报告说，ADAR1p110调节R-环的形成和基因组的稳定性在端粒癌细胞携带非典型的端粒重复序列的变体。ADAR1p110编辑RNA内的A-C错配：在典型和非典型变异重复序列之间形成的DNA杂合体。将A-C错配编辑为I：C匹配对有助于通过RNA酶H2解析端粒R环。端粒R环的这种ADAR1p110依赖性控制是端粒酶再活化癌细胞持续增殖所必需的，揭示了ADAR1p110的促癌性质，并将ADAR1鉴定为端粒酶阳性癌症的有希望的治疗靶点。一种类型的RNA编辑涉及ADAR介导的腺苷向肌苷的转化。在这里，作者表明ADAR 1核亚型p110调节癌细胞端粒的R环形成和基因组稳定性。
ADAR1 is involved in adenosine-to-inosine RNA editing. The cytoplasmic ADAR1p150 edits 3’UTR double-stranded RNAs and thereby suppresses induction of interferons. Loss of this ADAR1p150 function underlies the embryonic lethality of Adar1 null mice, pathogenesis of the severe autoimmune disease Aicardi-Goutières syndrome, and the resistance developed in cancers to immune checkpoint blockade. In contrast, the biological functions of the nuclear-localized ADAR1p110 remain largely unknown. Here, we report that ADAR1p110 regulates R-loop formation and genome stability at telomeres in cancer cells carrying non-canonical variants of telomeric repeats. ADAR1p110 edits the A-C mismatches within RNA:DNA hybrids formed between canonical and non-canonical variant repeats. Editing of A-C mismatches to I:C matched pairs facilitates resolution of telomeric R-loops by RNase H2. This ADAR1p110-dependent control of telomeric R-loops is required for continued proliferation of telomerase-reactivated cancer cells, revealing the pro-oncogenic nature of ADAR1p110 and identifying ADAR1 as a promising therapeutic target of telomerase positive cancers. One type of RNA editing involves ADAR-mediated conversion of adenosine to inosine. Here the authors show that ADAR1 nuclear isoform p110 regulates R loop formation and genome stability at telomeres in cancer cells.
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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：
14.9
作者：
Chon H;Sparks JL;Rychlik M;Nowotny M;Burgers PM;Crouch RJ;Cerritelli SM
通讯作者：
Cerritelli SM
影响因子：
64.8
作者：
Ishizuka, Jeffrey J.;Manguso, Robert T.;Haining, W. Nicholas
通讯作者：
Haining, W. Nicholas
转录复制冲突取向调节R环水平并激活不同的DNA损伤反应。
影响因子：
64.5
作者：
Hamperl S;Bocek MJ;Saldivar JC;Swigut T;Cimprich KA
通讯作者：
Cimprich KA
影响因子：
16.6
作者：
Eggington, Julie M.;Greene, Tom;Bass, Brenda L.
通讯作者：
Bass, Brenda L.