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

Hao-Ming Chang, Natalia J. Martinez, James E. Thornton, John P. Hagan, Khang D. Nguyen and Richard I. Gregory ()
Additional contact information
Hao-Ming Chang: Stem Cell Program, Children's Hospital Boston, Harvard Medical School, Harvard Stem Cell Institute
Natalia J. Martinez: Stem Cell Program, Children's Hospital Boston, Harvard Medical School, Harvard Stem Cell Institute
James E. Thornton: Stem Cell Program, Children's Hospital Boston, Harvard Medical School, Harvard Stem Cell Institute
John P. Hagan: Stem Cell Program, Children's Hospital Boston, Harvard Medical School, Harvard Stem Cell Institute
Khang D. Nguyen: Stem Cell Program, Children's Hospital Boston, Harvard Medical School, Harvard Stem Cell Institute
Richard I. Gregory: Stem Cell Program, Children's Hospital Boston, Harvard Medical School, Harvard Stem Cell Institute

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: 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.

Date: 2012
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms1909 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1909

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1909

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().