A Family of Argonaute-Interacting Proteins Gates Nuclear RNAi.

Autor:	Lewis A; Department of Biochemistry & Goodman Cancer Research Centre, McGill University, Montréal, QC H3A 1A3, Canada., Berkyurek AC; Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK., Greiner A; Molecular Cell Biology and Genetics, Max Planck Institute, 01307 Dresden, Germany., Sawh AN; Department of Biochemistry & Goodman Cancer Research Centre, McGill University, Montréal, QC H3A 1A3, Canada., Vashisht A; Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Merrett S; Molecular Cell Biology and Genetics, Max Planck Institute, 01307 Dresden, Germany., Flamand MN; Department of Biochemistry & Goodman Cancer Research Centre, McGill University, Montréal, QC H3A 1A3, Canada., Wohlschlegel J; Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Sarov M; Molecular Cell Biology and Genetics, Max Planck Institute, 01307 Dresden, Germany., Miska EA; Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK., Duchaine TF; Department of Biochemistry & Goodman Cancer Research Centre, McGill University, Montréal, QC H3A 1A3, Canada. Electronic address: thomas.duchaine@mcgill.ca.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2020 Jun 04; Vol. 78 (5), pp. 862-875.e8. Date of Electronic Publication: 2020 Apr 28.
DOI:	10.1016/j.molcel.2020.04.007
Abstrakt:	Nuclear RNA interference (RNAi) pathways work together with histone modifications to regulate gene expression and enact an adaptive response to transposable RNA elements. In the germline, nuclear RNAi can lead to trans-generational epigenetic inheritance (TEI) of gene silencing. We identified and characterized a family of nuclear Argonaute-interacting proteins (ENRIs) that control the strength and target specificity of nuclear RNAi in C. elegans, ensuring faithful inheritance of epigenetic memories. ENRI-1/2 prevent misloading of the nuclear Argonaute NRDE-3 with small RNAs that normally effect maternal piRNAs, which prevents precocious nuclear translocation of NRDE-3 in the early embryo. Additionally, they are negative regulators of nuclear RNAi triggered from exogenous sources. Loss of ENRI-3, an unstable protein expressed mostly in the male germline, misdirects the RNAi response to transposable elements and impairs TEI. The ENRIs determine the potency and specificity of nuclear RNAi responses by gating small RNAs into specific nuclear Argonautes. Competing Interests: Declaration of Interests E.A.M. is a founder and director of STORM Therapeutics. This company has not contributed to this research in any way. The authors declare no competing interests. (Copyright © 2020. Published by Elsevier Inc.)
Databáze:	MEDLINE
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