A first exon termination checkpoint preferentially suppresses extragenic transcription.
A first exon termination checkpoint preferentially suppresses extragenic transcription.
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DOI：
10.1038/s41594-021-00572-y
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发表时间：
2021-04
影响因子：
16.8
通讯作者：
Natoli G
中科院分区：
文献类型：
--
作者：
Austenaa LMI;Piccolo V;Russo M;Prosperini E;Polletti S;Polizzese D;Ghisletti S;Barozzi I;Diaferia GR;Natoli G
剪接机制和RNA聚合酶II（RNA Pol II）之间的相互作用增加了蛋白质编码基因的转录。类似地，增强子产生的lncRNA（elncRNA）的外显子和剪接信号增强增强子活性。然而，elncRNA的剪接效率低下，这表明与蛋白质编码基因相比，它们含有性质不同的外显子，驱动剪接的能力有限。我们在这里表明，在人类和小鼠细胞中，elncRNA以及启动子反义lncRNA（pa-lncRNA）的第一外显子的低效剪接触发了一个转录终止检查点，需要WDR 82，RNA Pol II结合蛋白，及其先前未知功能的RNA结合伴侣，ZC 3 H4。我们建议，第一外显子的elncRNA和pa-lncRNA的一个内在的组成部分的监管机制，一方面最大限度地提高这些顺式调节元件的活性，通过招募剪接机器，另一方面包含元件，抑制普遍的基因外转录。
Interactions between the splicing machinery and RNA Polymerase II (RNA Pol II) increase protein-coding gene transcription. Similarly, exons and splicing signals of enhancer-generated lncRNAs (elncRNAs) augment enhancer activity. However, elncRNAs are inefficiently spliced, suggesting that compared to protein-coding genes they contain qualitatively different exons with a limited ability to drive splicing. We show here that the inefficiently spliced first exons of elncRNAs as well as promoter-antisense lncRNAs (pa-lncRNAs) in human and mouse cells trigger a transcription termination checkpoint that requires WDR82, an RNA Pol II-binding protein, and its RNA-binding partner of previously unknown function, ZC3H4. We propose that the first exons of elncRNAs and pa-lncRNAs are an intrinsic component of a regulatory mechanism that on the one hand maximizes the activity of these cis-regulatory elements by recruiting the splicing machinery, and on the other contains elements that suppress pervasive extragenic transcription.
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影响因子：
9.3
作者：
Gil, Noa;Ulitsky, Igor
通讯作者：
Ulitsky, Igor
影响因子：
10.5
作者：
FRIDELL, RA;PRET, AM;SEARLES, LL
通讯作者：
SEARLES, LL
影响因子：
12.3
作者：
Cáceres EF;Hurst LD
通讯作者：
Hurst LD
DOI：
10.1126/science.1259418
发表时间：
2015-02-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arner E;Daub CO;Vitting-Seerup K;Andersson R;Lilje B;Drabløs F;Lennartsson A;Rönnerblad M;Hrydziuszko O;Vitezic M;Freeman TC;Alhendi AM;Arner P;Axton R;Baillie JK;Beckhouse A;Bodega B;Briggs J;Brombacher F;Davis M;Detmar M;Ehrlund A;Endoh M;Eslami A;Fagiolini M;Fairbairn L;Faulkner GJ;Ferrai C;Fisher ME;Forrester L;Goldowitz D;Guler R;Ha T;Hara M;Herlyn M;Ikawa T;Kai C;Kawamoto H;Khachigian LM;Klinken SP;Kojima S;Koseki H;Klein S;Mejhert N;Miyaguchi K;Mizuno Y;Morimoto M;Morris KJ;Mummery C;Nakachi Y;Ogishima S;Okada-Hatakeyama M;Okazaki Y;Orlando V;Ovchinnikov D;Passier R;Patrikakis M;Pombo A;Qin XY;Roy S;Sato H;Savvi S;Saxena A;Schwegmann A;Sugiyama D;Swoboda R;Tanaka H;Tomoiu A;Winteringham LN;Wolvetang E;Yanagi-Mizuochi C;Yoneda M;Zabierowski S;Zhang P;Abugessaisa I;Bertin N;Diehl AD;Fukuda S;Furuno M;Harshbarger J;Hasegawa A;Hori F;Ishikawa-Kato S;Ishizu Y;Itoh M;Kawashima T;Kojima M;Kondo N;Lizio M;Meehan TF;Mungall CJ;Murata M;Nishiyori-Sueki H;Sahin S;Nagao-Sato S;Severin J;de Hoon MJ;Kawai J;Kasukawa T;Lassmann T;Suzuki H;Kawaji H;Summers KM;Wells C;FANTOM Consortium;Hume DA;Forrest AR;Sandelin A;Carninci P;Hayashizaki Y
通讯作者：
Hayashizaki Y
影响因子：
64.8
作者：
Engreitz JM;Haines JE;Perez EM;Munson G;Chen J;Kane M;McDonel PE;Guttman M;Lander ES
通讯作者：
Lander ES