A family of C. elegans VASA homologs control Argonaute pathway specificity and promote transgenerational silencing.

Autor:	Dai S; RNA Therapeutic Institute, UMass Chan Medical School, Worcester, MA 01605, USA; Morningside Graduate School of Biomedical Sciences, UMass Chan Medical School, Worcester, MA 01605, USA., Tang X; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China., Li L; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China., Ishidate T; RNA Therapeutic Institute, UMass Chan Medical School, Worcester, MA 01605, USA., Ozturk AR; RNA Therapeutic Institute, UMass Chan Medical School, Worcester, MA 01605, USA., Chen H; Program in Bioinformatics and Integrative Biology, UMass Chan Medical School, Worcester, MA 01605, USA; Bioinformatics Program, Boston University, Boston, MA 02215, USA., Dude AL; RNA Therapeutic Institute, UMass Chan Medical School, Worcester, MA 01605, USA., Yan YH; National Institute of Biological Sciences, Beijing 102206, China., Dong MQ; National Institute of Biological Sciences, Beijing 102206, China., Shen EZ; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China. Electronic address: shenenzhi@westlake.edu.cn., Mello CC; RNA Therapeutic Institute, UMass Chan Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA. Electronic address: craig.mello@umassmed.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Sep 06; Vol. 40 (10), pp. 111265.
DOI:	10.1016/j.celrep.2022.111265
Abstrakt:	Germline Argonautes direct transcriptome surveillance within perinuclear membraneless organelles called nuage. In C. elegans, a family of Vasa-related Germ Line Helicase (GLH) proteins localize in and promote the formation of nuage. Previous studies have implicated GLH proteins in inherited silencing, but direct roles in small-RNA production, Argonaute binding, or mRNA targeting have not been identified. Here we show that GLH proteins compete with each other to control Argonaute pathway specificity, bind directly to Argonaute target mRNAs, and promote the amplification of small RNAs required for transgenerational inheritance. We show that the ATPase cycle of GLH-1 regulates direct binding to the Argonaute WAGO-1, which engages amplified small RNAs. Our findings support a dynamic and direct role for GLH proteins in inherited silencing beyond their role as structural components of nuage. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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