Chang, Hao-MingMartinez, Natalia JThornton, James EdwardGregory, Richard2013-04-242012Chang, Hao-Ming, Natalia J. Martinez, James Edward Thornton, and Richard Ian Gregory. 2012. Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation. Nature Communications 3(6): 923.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:10581968Pluripotent embryonic stem cells (ESCs) have a shortened cell cycle that enables their rapid proliferation. The ESC-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 ESCs. Here, to gain further insight into mechanisms controlling ESC self-renewal we explore the molecular and cellular role of the let-7 target Trim71 (mLin41). We show that Trim71 associates with Argonaute2 (Ago2) 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 Ago2, localization to P-bodies, and for repression of reporter mRNAs. Trim71 knockdown prolongs the G1 phase of the cell cycle and slows ESC proliferation, a phenotype that was rescued by depletion of Cdkn1a. Thus, we demonstrate Trim71 is a factor that facilitates the G1–S transition to promote rapid ESC self-renewal.en-USbiological sciencescell biologymolecular biologyJournal Article2013-04-2410.1038/ncomms1909