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启动子反义RNA的形状调节配体诱导的转录激活
2021-07-04 13:55

美国加州大学圣迭戈分校Michael G. Rosenfeld、Fan Yang等研究人员合作发现,启动子反义RNA的形状调节配体诱导的转录激活。2021年6月30日,《自然》杂志在线发表了这项成果。

研究人员报告了一种检测方法的开发——称为RNA-Cas13a复合物介导的染色质分离——可用于定量检测基因组中RNA的分布。该测定表明,启动子反义(PAS)RNA是广泛转录暂停释放程序的关键因子。通过配体ERα诱导的PAS RNA导致H3K9me3的显著丢失以及在激活的靶基因启动子上释放基础招募的HP1α和KAP1。这种释放是由于H3K9me3去甲基化酶的PAS RNA依赖性招募,这需要与PAS RNA中紧凑的茎环结构相互作用,这是类似调节的PAS RNA的一个明显特征。

ERα结合的MegaTrans增强子的激活(对于稳健的暂停释放至关重要)需要招募磷酸化的KAP1,并将其转移到同源启动子,从而促进17β-雌二醇诱导的暂停释放和靶基因激活。这项研究揭示了一种基于RNA结构的机制,该机制介导PAS RNA在基因调控中的功能。

据了解,哺乳动物基因组中长链非编码RNA转录程序的大小引发了对其生物学作用的讨论,特别是PAS转录本。

附:英文原文

Title: Shape of promoter antisense RNAs regulates ligand-induced transcription activation

Author: Fan Yang, Bogdan Tanasa, Rudi Micheletti, Kenneth A. Ohgi, Aneel K. Aggarwal, Michael G. Rosenfeld

Issue&Volume: 2021-06-30

Abstract: The size of the transcriptional program of long non-coding RNAs in the mammalian genome has engendered discussions about their biological roles1, particularly the promoter antisense (PAS) transcripts2,3. Here we report the development of an assay—referred to as chromatin isolation by RNA–Cas13a complex—to quantitatively detect the distribution of RNA in the genome. The assay revealed that PAS RNAs serve as a key gatekeeper of a broad transcriptional pause release program, based on decommissioning the 7SK small nuclear RNA-dependent inhibitory P-TEFb complex. Induction of PAS RNAs by liganded ERα led to a significant loss of H3K9me3 and the release of basally recruited HP1α and KAP1 on activated target gene promoters. This release was due to PAS RNA-dependent recruitment of H3K9me3 demethylases, which required interactions with a compact stem-loop structure in the PAS RNAs, an apparent feature of similarly regulated PAS RNAs. Activation of the ERα-bound MegaTrans enhancer, which is essential for robust pause release, required the recruitment of phosphorylated KAP1, with its transfer to the cognate promoters permitting 17β-oestradiol-induced pause release and activation of the target gene. This study reveals a mechanism, based on RNA structure, that mediates the function of PAS RNAs in gene regulation.

DOI: 10.1038/s41586-021-03589-x

Source: https://www.nature.com/articles/s41586-021-03589-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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