Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons.
Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons.
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DOI：
10.1038/ncomms5760
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发表时间：
2014-09-11
影响因子：
16.6
通讯作者：
Elliott, David J.
中科院分区：
文献类型：
--
作者：
Best, Andrew;James, Katherine;Dalgliesh, Caroline;Hong, Elaine;Kheirolahi-Kouhestani, Mahsa;Curk, Tomaz;Xu, Yaobo;Danilenko, Marina;Hussain, Rafiq;Keavney, Bernard;Wipat, Anil;Klinck, Roscoe;Cowell, Ian G.;Lee, Ka Cheong;Austin, Caroline A.;Venables, Julian P.;Chabot, Benoit;Koref, Mauro Santibanez;Tyson-Capper, Alison;Elliott, David J.
选择性剪接（从单个基因产生多种信使 RNA 同工型）部分受到 RNA 结合蛋白的调节。虽然 RBP 变压器 2 α (Tra2α) 和 Tra2β 都与选择性剪接的调节有关，但它们对此过程的相对贡献尚不清楚。在这里，我们发现 Tra2α 和 Tra2β 同时（但不是单独）耗尽会导致内源 Tra2β 靶外显子剪接发生实质性变化，并且组成型和替代靶外显子都受到 Tra2α-Tra2β 双重控制。靶外显子富含与染色体生物学相关的基因，包括编码关键 DNA 损伤反应蛋白的 CHEK1。双 Tra2 蛋白耗尽会降低全长 CHK1 蛋白的表达，导致 DNA 损伤标记 γH2AX 的积累并降低细胞活力。我们得出结论，Tra2 蛋白通过旁系同源补偿共同控制组成型和选择性剪接模式，以控制维持细胞活力所必需的途径。 RNA 结合蛋白是选择性剪接的关键调节因子。在这里，贝斯特等人。研究表明，人类 Tra2α 和 Tra2ß RNA 结合蛋白共同有助于控制组成型和选择性剪接事件，以调节重要的生物过程，包括对 DNA 损伤的反应。
Alternative splicing—the production of multiple messenger RNA isoforms from a single gene—is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2β have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous—but not individual—depletion of Tra2α and Tra2β induces substantial shifts in splicing of endogenous Tra2β target exons, and that both constitutive and alternative target exons are under dual Tra2α–Tra2β control. Target exons are enriched in genes associated with chromosome biology including CHEK1, which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability. RNA binding proteins are key regulators of alternative splicing. Here, Best et al. show that the human Tra2α and Tra2ß RNA binding proteins jointly contribute to the control of constitutive and alternative splicing events to regulate essential biological processes including the response to DNA damage.
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影响因子：
3.9
作者：
Elliott DJ;Best A;Dalgliesh C;Ehrmann I;Grellscheid S
通讯作者：
Grellscheid S
影响因子：
7.3
作者：
Busch, Anke;Hertel, Klemens J.
通讯作者：
Hertel, Klemens J.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
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
影响因子：
16.8
作者：
Clery, Antoine;Jayne, Sandrine;Allain, Frederic H-T
通讯作者：
Allain, Frederic H-T