期刊
RNA BIOLOGY
卷 13, 期 3, 页码 272-278出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2016.1142039
关键词
spliceosome; DDR signaling; Alternative splicing; UV irradiation; transcription; ATM; DNA damage; R-loops
资金
- European Research Council (ERC) [340988] Funding Source: European Research Council (ERC)
- European Research Council [340988] Funding Source: Medline
In response to DNA damage cells activate intricate protein networks to ensure genomic fidelity and tissue homeostasis. DNA damage response signaling pathways coordinate these networks and determine cellular fates, in part, by modulating RNA metabolism. Here we discuss a replication-independent pathway activated by transcription-blocking DNA lesions, which utilizes the ATM signaling kinase to regulate spliceosome function in a reciprocal manner. We present a model according to which, displacement of co-transcriptional spliceosomes from lesion-arrested RNA polymerases, culminates in R-loop formation and non-canonical ATM activation. ATM signals in a feed-forward fashion to further impede spliceosome organization and regulates UV-induced gene expression and alternative splicing genome-wide. This reciprocal coupling between ATM and the spliceosome highlights the importance of ATM signaling in the cellular response to transcription-blocking lesions and supports a key role of the splicing machinery in this process.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据