Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation

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Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation

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Title: Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
Author: Chang, Hao-Ming; Martinez, Natalia J; Thornton, James Edward; Gregory, Richard Ian

Note: Order does not necessarily reflect citation order of authors.

Citation: Chang, 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.
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Abstract: Pluripotent 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.
Published Version: doi:10.1038/ncomms1909
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518406/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10581968
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