A Family of Argonaute-Interacting Proteins Gates Nuclear RNAi.

Abstract:

: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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Lewis A,Berkyurek AC,Greiner A,Sawh AN,Vashisht A,Merrett S,Flamand MN,Wohlschlegel J,Sarov M,Miska EA,Duchaine TF

doi

10.1016/j.molcel.2020.04.007

subject

Has Abstract

pub_date

2020-06-04 00:00:00

pages

862-875.e8

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(20)30233-1

journal_volume

78

pub_type

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