Argonaute-miRNA Complexes Silence Target MRNAs in the Nucleus of Mammalian Stem Cells

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Aug 28

PMID 30146314

Citations 59

Authors

Aishe A Sarshad

Aster H Juan

Ana Iris Correa Muler

Dimitrios G Anastasakis

Xiantao Wang

Pavol Genzor

Xuesong Feng

Pei-Fang Tsai

Hong-Wei Sun

Astrid D Haase

Vittorio Sartorelli

Markus Hafner

Affiliations

Soon will be listed here.

Abstract

In mammals, gene silencing by the RNA-induced silencing complex (RISC) is a well-understood cytoplasmic posttranscriptional gene regulatory mechanism. Here, we show that embryonic stem cells (ESCs) contain high levels of nuclear AGO proteins and that in ESCs nuclear AGO protein activity allows for the onset of differentiation. In the nucleus, AGO proteins interact with core RISC components, including the TNRC6 proteins and the CCR4-NOT deadenylase complex. In contrast to cytoplasmic miRNA-mediated gene silencing that mainly operates on cis-acting elements in mRNA 3' untranslated (UTR) sequences, in the nucleus AGO binding in the coding sequence and potentially introns also contributed to post-transcriptional gene silencing. Thus, nuclear localization of AGO proteins in specific cell types leads to a previously unappreciated expansion of the miRNA-regulated transcriptome.

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