Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism.
Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism.
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哺乳动物 APE1 控制 miRNA 加工，其相互作用组与癌症 RNA 代谢相关
DOI：
10.1038/s41467-017-00842-8
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发表时间：
2017-10-06
影响因子：
16.6
通讯作者：
Tell G
中科院分区：
文献类型：
--
作者：
Antoniali G;Serra F;Lirussi L;Tanaka M;D'Ambrosio C;Zhang S;Radovic S;Dalla E;Ciani Y;Scaloni A;Li M;Piazza S;Tell G
哺乳动物脱嘌呤/脱嘧啶核酸内切酶1是一种DNA修复酶，参与基因组的稳定性和氧化应激反应、肿瘤进展和化疗耐药相关基因的表达。然而，脱嘌呤/脱嘧啶核酸内切酶1在这些过程中的作用的分子机制仍然不清楚。最近的发现指出了脱嘌呤/脱嘧啶核酸内切酶1在RNA代谢中的一个新的作用。通过对脱嘌呤/脱嘧啶内切酶1与RNA和其他蛋白质相互作用的表征，我们在这里证明了脱嘌呤/脱嘧啶内切酶1在pri-miRNA加工中的作用和在遗传毒性胁迫中通过与DROSHA加工复合体结合而保持稳定的作用。我们还发现，在miR-221/222调控肿瘤抑制基因PTEN表达的过程中，脱嘌呤/脱嘧啶内切酶1的内切酶活性是必需的。对不同癌症队列的分析支持了我们的发现与肿瘤生物学的相关性。我们还发现，脱嘌呤/脱嘧啶核酸内切酶1参与了与癌症发生有关的RNA相互作用和蛋白质相互作用，从而表明对癌症基因具有意想不到的转录后效应。
Mammalian apurinic/apyrimidinic endonuclease 1 is a DNA repair enzyme involved in genome stability and expression of genes involved in oxidative stress responses, tumor progression and chemoresistance. However, the molecular mechanisms underlying the role of apurinic/apyrimidinic endonuclease 1 in these processes are still unclear. Recent findings point to a novel role of apurinic/apyrimidinic endonuclease 1 in RNA metabolism. Through the characterization of the interactomes of apurinic/apyrimidinic endonuclease 1 with RNA and other proteins, we demonstrate here a role for apurinic/apyrimidinic endonuclease 1 in pri-miRNA processing and stability via association with the DROSHA-processing complex during genotoxic stress. We also show that endonuclease activity of apurinic/apyrimidinic endonuclease 1 is required for the processing of miR-221/222 in regulating expression of the tumor suppressor PTEN. Analysis of a cohort of different cancers supports the relevance of our findings for tumor biology. We also show that apurinic/apyrimidinic endonuclease 1 participates in RNA-interactomes and protein-interactomes involved in cancer development, thus indicating an unsuspected post-transcriptional effect on cancer genes.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
影响因子：
2.5
作者：
Howe EN;Cochrane DR;Richer JK
通讯作者：
Richer JK
影响因子：
5.6
作者：
Berquist, Brian R.;McNeill, Daniel R.;Wilson, David M., III
通讯作者：
Wilson, David M., III
影响因子：
3.7
作者：
Cesaratto L;Codarin E;Vascotto C;Leonardi A;Kelley MR;Tiribelli C;Tell G
通讯作者：
Tell G
影响因子：
2.5
作者：
Garofalo M;Quintavalle C;Romano G;Croce CM;Condorelli G
通讯作者：
Condorelli G