Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways.
Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways.
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ADAR1结合的基因组分析及其参与多个RNA处理途径。
DOI：
10.1038/ncomms7355
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发表时间：
2015-03-09
影响因子：
16.6
通讯作者：
Xiao, Xinshu
中科院分区：
文献类型：
--
作者：
Bahn, Jae Hoon;Ahn, Jaegyoon;Lin, Xianzhi;Zhang, Qing;Lee, Jae-Hyung;Civelek, Mete;Xiao, Xinshu
作用于RNA的腺苷脱氨酶（ADARs）是后生动物中腺苷到肌苷（A-to-I）编辑的主要因素。在这里，我们报告了首次使用CLIP-Seq对人类细胞中ADAR1-RNA相互作用的全球研究。在Alu重复序列中观察到大量的CLIP位点，这与ADAR1在RNA编辑中的功能一致。令人惊讶的是，数千个其他CLIP位点位于非alu区域，揭示了ADAR1在调节替代3' UTR使用和miRNA生物发生中的功能和生物物理靶点。我们观察到ADAR1与3' UTR的结合排除了其他因子的结合，导致3' UTR延长。同样，ADAR1在细胞核中与DROSHA和DGCR8相互作用，并可能在初级miRNA结合中胜过DGCR8，从而增强成熟miRNA的表达。这些功能依赖于ADAR1的编辑活动，至少对于目标子集是这样。我们的研究揭示了ADAR1的功能作用的广阔前景。
Adenosine deaminases acting on RNA (ADARs) are the primary factors underlying adenosine to inosine (A-to-I) editing in metazoans. Here we report the first global study of ADAR1-RNA interaction in human cells using CLIP-Seq. A large number of CLIP sites are observed in Alu repeats, consistent with ADAR1's function in RNA editing. Surprisingly, thousands of other CLIP sites are located in non-Alu regions, revealing functional and biophysical targets of ADAR1 in the regulation of alternative 3' UTR usage and miRNA biogenesis. We observe that binding of ADAR1 to 3' UTRs precludes binding by other factors, causing 3' UTR lengthening. Similarly, ADAR1 interacts with DROSHA and DGCR8 in the nucleus and possibly out-competes DGCR8 in primary miRNA binding, which enhances mature miRNA expression. These functions are dependent on ADAR1's editing activity, at least for a subset of targets. Our study unfolds a broad landscape of the functional roles of ADAR1.
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影响因子：
1.7
作者：
Jurka, J;Kapitonov, VV;Walichiewicz, J
通讯作者：
Walichiewicz, J
影响因子：
9.8
作者：
Edwards, SM;Kote-Jarai, Z;Eeles, RA
通讯作者：
Eeles, RA
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W