| First Author | Chang HM | Year | 2012 |
| Journal | Nat Commun | Volume | 3 |
| Pages | 923 | PubMed ID | 22735451 |
| Mgi Jnum | J:190251 | Mgi Id | MGI:5448492 |
| Doi | 10.1038/ncomms1909 | Citation | Chang HM, et al. (2012) Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation. Nat Commun 3:923 |
| abstractText | 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. |
