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Title:
Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation | Nature Communications
Description:
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 G1โS 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 G1โS transition to promote rapid embryonic stem cell self-renewal. Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1โS phase cell cycle transition in embryonic stem cells.
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headline:Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
description: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 G1รขยยS 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 G1รขยยS transition to promote rapid embryonic stem cell self-renewal. Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1รขยยS phase cell cycle transition in embryonic stem cells.
datePublished:2012-06-26T00:00:00Z
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description: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 G1รขยยS 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 G1รขยยS transition to promote rapid embryonic stem cell self-renewal. Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1รขยยS phase cell cycle transition in embryonic stem cells.
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