Yangming W, W. and Collin M.;, M. and Li Ya-Pu, , and Shenoy A.; , A. and Zhang Xin-Xin, , and Subramanyam, D. and Robert , B. (2013) MiR-294/-302 promotes proliferation, suppresses G1-S restriction point, and inhibits embryonic stem cell differentiation through separable mechanisms. Cell Rep. 2013 July 11; 4(1): 99–109, 4 (1). pp. 99-109.

Text 63. Dr. Deepa S. (Cell Rep.) Author Copy on BMC-Open Access.pdf - Accepted Version Restricted to Registered users only Download (693Kb) | Request a copy

Abstract

The miR-294/miR-302 microRNAs promote the abbreviated G1 phase of the embryonic stem cell (ESC) cell cycle and suppress differentiation induced by let-7. Here we evaluated the role of the Retinoblastoma (Rb) family proteins in these settings. Under normal growth conditions miR-294 promoted the rapid G1-S transition independent of the Rb family. In contrast, miR-294 suppressed the further accumulation of cells in G1 in response to nutrient deprivation and cell-cell contact in an Rb dependent fashion. We uncovered five additional miRNAs (miRs-26a, -99b, -193, -199a-5p, and 218) that silenced ESC self-renewal in the absence of other miRNAs, all of which were antagonized by miR-294/302. Four of the six differentiation-inducing miRNAs induced an Rbdependent G1 accumulation. However, all six still silenced self-renewal in the absence of the Rb proteins. These results show that the miR-294/miR-302 family acts through Rb dependent and independent pathways to regulate the G1 restriction point and the silencing of self-renewal respectively.

Item Type:	Article
Subjects:	Stem Cell Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	27 Apr 2015 10:51
Last Modified:	02 Jul 2015 06:10
URI:	http://nccs.sciencecentral.in/id/eprint/143

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