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SERRATE 的相分离驱动体切割体的组装,并促进拟南芥 miRNA 的加工。

Phase separation of SERRATE drives dicing body assembly and promotes miRNA processing in Arabidopsis.

机构信息

Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing, China.

Tsinghua-Peking Center for Life Sciences, Beijing, China.

出版信息

Nat Cell Biol. 2021 Jan;23(1):32-39. doi: 10.1038/s41556-020-00606-5. Epub 2020 Dec 7.

Abstract

MicroRNA (miRNA) production entails the step-wise processing of primary miRNAs (pri-miRNAs) into precursor miRNAs (pre-miRNAs) and miRNA/* duplexes by Dicing complexes containing DCL1, HYL1 and SE, which are localized in nuclear dicing bodies (D-bodies). Here, we show that D-bodies are phase-separated condensates. SE forms droplets and drives DCL1, HYL1 and pri/pre-miRNAs into the droplets in vitro, and mutation of SE abrogates the formation of D-bodies in vivo, which indicates that D-bodies arise through SE-mediated phase separation. Disruption of SE phase separation greatly reduces its activity in promoting miRNA processing both in vitro and in vivo. We further show that pre-miRNAs are processed into miRNA/* duplexes in the droplets and, after processing, miRNA/* duplexes are bound by HYL1 and released from the droplets. Our findings provide evidence that efficient miRNA processing depends on the SE-phase-separation-mediated formation of D-bodies and suggest a paradigm that the products made in phase-separated condensates can be shipped out for subsequent processes.

摘要

MicroRNA (miRNA) 的生成需要 Dicer 复合物逐步加工初级 miRNA (pri-miRNA) 成为前体 miRNA (pre-miRNA) 和 miRNA/*双链,该复合物包含 DCL1、HYL1 和 SE,定位于核 Dicer 体 (D-body) 中。在这里,我们表明 D-body 是相分离的凝聚物。SE 形成液滴,并在体外将 DCL1、HYL1 和 pri/pre-miRNA 驱动到液滴中,而 SE 的突变会在体内破坏 D-body 的形成,这表明 D-body 是通过 SE 介导的相分离形成的。SE 相分离的破坏极大地降低了其在体外和体内促进 miRNA 加工的活性。我们进一步表明,pre-miRNA 在液滴中被加工成 miRNA/*双链,并且在加工后,miRNA/*双链被 HYL1 结合并从液滴中释放出来。我们的发现提供了证据表明有效的 miRNA 加工取决于 SE 相分离介导的 D-body 的形成,并提出了一个范例,即在相分离凝聚物中产生的产物可以被运出以供后续处理。

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