Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
Open Access
- 1 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 3 (1), 1-10
- https://doi.org/10.1038/ncomms1909
Abstract
Pluripotent embryonic stem cells have a shortened cell cycle that enables their rapid proliferation. The embryonic stem cell-specific miR-290 and miR-302 microRNA families promote proliferation whereas let-7 microRNAs inhibit self-renewal, and promote cell differentiation. Lin28 suppresses let-7 expression in embryonic stem cells. Here to gain further insight into mechanisms controlling embryonic stem cell self-renewal, we explore the molecular and cellular role of the let-7 target Trim71 (mLin41). We show that Trim71 associates with Argonaute2 and microRNAs, and represses expression of Cdkn1a, a cyclin-dependent kinase inhibitor that negatively regulates the G1–S transition. We identify protein domains required for Trim71 association with Argonaute2, localization to P-bodies, and for repression of reporter messenger RNAs. Trim71 knockdown prolongs the G1 phase of the cell cycle and slows embryonic stem cell proliferation, a phenotype that was rescued by depletion of Cdkn1a. Thus, we demonstrate that Trim71 is a factor that facilitates the G1–S transition to promote rapid embryonic stem cell self-renewal.This publication has 42 references indexed in Scilit:
- Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to PluripotencyCell Stem Cell, 2011
- Opposing microRNA families regulate self-renewal in mouse embryonic stem cellsNature, 2010
- Direct cell reprogramming is a stochastic process amenable to accelerationNature, 2009
- nhl-2 Modulates MicroRNA Activity in Caenorhabditis elegansCell, 2009
- The TRIM-NHL Protein TRIM32 Activates MicroRNAs and Prevents Self-Renewal in Mouse Neural ProgenitorsCell, 2009
- Embryonic stem cell–specific microRNAs regulate the G1-S transition and promote rapid proliferationNature Genetics, 2008
- Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNAMolecular Cell, 2008
- Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineageNature, 2008
- DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewalNature Genetics, 2007
- Functional Proteomics Reveals the Biochemical Niche of C. elegans DCR-1 in Multiple Small-RNA-Mediated PathwaysCell, 2006