由紫外線輻射引入到DNA內(nèi)的損傷會(huì)阻斷轉(zhuǎn)錄，這是一個(gè)也被用來(lái)下調(diào)蛋白豐度的機(jī)制。這一DNA損傷反應(yīng)已知也會(huì)影響轉(zhuǎn)錄體剪接，而這項(xiàng)研究則提出一個(gè)可能的機(jī)制。Maria Tresini及同事發(fā)現(xiàn)，紫外線損傷造成含有U2和U5 snRNP的核心剪接體的染色質(zhì)置換，因此，會(huì)形成含有新轉(zhuǎn)錄體的R-環(huán)，后者以前饋方式激活DNA損傷反應(yīng)激酶ATM，來(lái)影響剪接體動(dòng)態(tài)和另類剪接。

原文對(duì)照：

In response to DNA damage, tissue homoeostasis is ensured by protein networks promoting DNA repair, cell cycle arrest or apoptosis. DNA damage response signalling pathways coordinate these processes, partly by propagating gene-expression-modulating signals. DNA damage influences not only the abundance of messenger RNAs, but also their coding information through alternative splicing. Here we show that transcription-blocking DNA lesions promote chromatin displacement of late-stage spliceosomes and initiate a positive feedback loop centred on the signalling kinase ATM. We propose that initial spliceosome displacement and subsequent R-loop formation is triggered by pausing of RNA polymerase at DNA lesions. In turn, R-loops activate ATM, which signals to impede spliceosome organization further and augment ultraviolet-irradiation-triggered alternative splicing at the genome-wide level. Our findings define R-loop-dependent ATM activation by transcription-blocking lesions as an important event in the DNA damage response of non-replicating cells, and highlight a key role for spliceosome displacement in this process.

原文地址：http://www.nature.com/nature/journal/v523/n7558/full/nature14512.html