U1 snRNP regulates chromatin retention of noncoding RNAs
U1 snRNP regulates chromatin retention of noncoding RNAs
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U1 snRNP 调节非编码 RNA 的染色质保留
DOI：
10.1038/s41586-020-2105-3
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发表时间：
2020
期刊：
影响因子：
64.8
通讯作者：
Shen Xiaohua
中科院分区：
文献类型：
--
作者：
Yin Yafei;Lu Yuyang;Zhang Xuechun;Shao Wen;Xu Yanhui;Li Pan;Hong Yantao;Cui Li;Shan Ge;Tian Bin;Zhang Qiangfeng Cliff;Shen Xiaohua
长链非编码rna （lncrna）和启动子或增强子相关的不稳定。转录本优先定位于染色质，其中一些调控染色质结构。转录和RNA加工1 - 13。尽管有几个RNA序列负责。已经确定了核定位-例如lncRNA Xist和Alu-like中的重复序列。长rnas14 - 16中的元素- lncRNAs作为一类如何在染色质上富集仍是未知的。在这里，我们描述了一种随机的、诱变耦合的、高通量的方法。我们将其命名为“通过测序进行亚细胞定位的RNA元件”（mutREL-seq）。利用这种方法，我们发现了一个识别U1小核的RNA基序。核糖核蛋白（snRNP），对报告rna定位到染色质至关重要。在整个基因组中，染色质结合的lncrna富含5 '剪接。3 '剪接位点的缺失，并表现出高水平的U1 snRNA结合。通过细胞质定位的信使rnaU1 snRNA或U1的急剧耗竭。snRNP蛋白组分SNRNP70显著降低。数百个lncrna和不稳定转录物，而不改变整体转录。细胞速率。此外，SNRNP70的快速降解降低了两者的定位。新生的和聚腺苷化的lncRNA转录成染色质，并破坏细胞核。以及lncRNA Malat1的全基因组定位。此外，U1 snRNP与。转录参与RNA聚合酶II。这些结果表明U1 snRNP起作用。以转录依赖的方式将lncrna广泛地连接和动员到染色质上。我们的发现揭示了U1 snRNP在细胞外的未知作用。前体mRNA的加工过程，并提供lncrna的分子机制。招募到调控位点执行染色质相关功能。
Long noncoding RNAs (lncRNAs) and promoter- or enhancer-associated unstable.transcripts locate preferentially to chromatin, where some regulate chromatin structure,.transcription and RNA processing1–13. Although several RNA sequences responsible for.nuclear localization have been identified—such as repeats in the lncRNA Xist and Alu-like.elements in long RNAs14–16—how lncRNAs as a class are enriched at chromatin remains.unknown. Here we describe a random, mutagenesis-coupled, high-throughput method.that we name ‘RNA elements for subcellular localization by sequencing’ (mutREL-seq)..Using this method, we discovered an RNA motif that recognizes the U1 small nuclear.ribonucleoprotein (snRNP) and is essential for the localization of reporter RNAs to.chromatin. Across the genome, chromatin-bound lncRNAs are enriched with 5′ splice.sites and depleted of 3′ splice sites, and exhibit high levels of U1 snRNA binding compared.with cytoplasm-localized messenger RNAs. Acute depletion of U1 snRNA or of the U1.snRNP protein component SNRNP70 markedly reduces the chromatin association of.hundreds of lncRNAs and unstable transcripts, without altering the overall transcription.rate in cells. In addition, rapid degradation of SNRNP70 reduces the localization of both.nascent and polyadenylated lncRNA transcripts to chromatin, and disrupts the nuclear.and genome-wide localization of the lncRNA Malat1. Moreover, U1 snRNP interacts with.transcriptionally engaged RNA polymerase II. These results show that U1 snRNP acts.widely to tether and mobilize lncRNAs to chromatin in a transcription-dependent.manner. Our findings have uncovered a previously unknown role of U1 snRNP beyond the.processing of precursor mRNA, and provide molecular insight into how lncRNAs are.recruited to regulatory sites to carry out chromatin-associated functions.