SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to impede miRNA production
SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to impede miRNA production
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DOI：
10.1038/s41586-018-0135-x
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发表时间：
2018-05-24
期刊：
影响因子：
64.8
通讯作者：
Zhang, Xiuren
中科院分区：
文献类型：
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作者：
Wang, Zhiye;Ma, Zeyang;Zhang, Xiuren
染色质重塑因子 (CHR) 通常用于改变染色质结构。 CHR 也存在于核糖核蛋白复合物中，但人们对其 RNA 相关功能知之甚少。在这里，我们表明 CHR2（也称为 BRM）是大开关/蔗糖不可发酵 (SWI/SNF) 复合物的 ATP 酶亚基，是微处理器组件 Serrate (SE) 的伙伴。 CHR2 促进初级 microRNA 前体 (pri-miRNA) 的转录，同时抑制体内 miRNA 的积累。 CHR2 转录后抑制 miRNA 积累需要与 SE 直接相互作用，但其转录活性则不需要。 CHR2可以直接结合并解旋pri-miRNA并抑制它们的加工，并且这种抑制需要CHR2在体外和体内的重塑和解旋酶活性。此外，野生型拟南芥和 chr2 突变体之间 pri-miRNA 的二级结构也不同。我们得出结论，CHR2 通过 SE 访问 pri-miRNA 并重塑其二级结构，从而阻止 DCL1 和 HYL1 的下游加工。我们的研究揭示了 pri-miRNA 作为 CHR2 的底物，以及微处理器活动上游控制 miRNA 积累的额外调节层。
Chromatin remodelling factors (CHRs) typically function to alter chromatin structure. CHRs also reside in ribonucleoprotein complexes, but little is known about their RNA-related functions. Here we show that CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE). CHR2 promotes the transcription of primary microRNA precursors (pri-miRNAs) while repressing miRNA accumulation in vivo. Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity. CHR2 can directly bind to and unwind pri-miRNAs and inhibit their processing, and this inhibition requires the remodelling and helicase activity of CHR2 in vitro and in vivo. Furthermore, the secondary structures of pri-miRNAs differed between wild-type Arabidopsis thaliana and chr2 mutants. We conclude that CHR2 accesses pri-miRNAs through SE and remodels their secondary structures, preventing downstream processing by DCL1 and HYL1. Our study uncovers pri-miRNAs as a substrate of CHR2, and an additional regulatory layer upstream of Microprocessor activity to control miRNA accumulation.