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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 G1βS 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 G1βS 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 G1βS phase cell cycle transition in embryonic stem cells.
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trim, cell, escs, pubmed, cells, article, cdkna, ago, fig, expression, lin, scholar, google, mirnas, cas, control, stem, proliferation, reporter, levels, protein, mouse, cycle, proteins, nature, rna, repression, esc, mirna, central, embryonic, domain, found, sirna, nhl, assays, differentiation, target, interaction, luciferase, data, knockdown, gene, performed, reverse, selfrenewal, activity, transfected, localization, utr,
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pew research scholar nature portfolio permissions reprints privacy policy advertising social media generate pflag-tnrc6b c-term32 ultraviolet-crosslinked dox-inducible escs nature 463 nature 454 nature 462 nature pflag-ms2-tnrc6b c-term full access multiple small-rna-mediated pathways high-affinity ms2-binding sites quantitative real-time pcr extended population-doubling time33 cyclin e-cdk2 complex34 tumor suppressor mei-p26 mirna-mediated gene regulation23 dox-inducible flag-trim71 escs cyclin e-cdk2 complex c57bl/6j genomic dna pflag-tnrc6b c-term ms2-tnrc6b c-terminus Ξ±-flag m2-peroxidase open biosystems author correspondence impairs p-body localization post-transcriptional gene repression unique cell-cycle structure es cell-specific mirna post-transcriptional gene silencing n-terminal flag-tag neuroprogenitor-based genetic subtype development mirna-induced silencing complex full size image edta-free bc-100 buffer edta-free bc buffer induce mirna-mediated repression embryonic stem cell pflag-trim71 full-length nonsense-mediated mrna decay mei-p26 regulates micrornas trim71-overexpressing cell populations amino-terminal ring finger post-transcriptionally repress expression n-terminal truncations interact
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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 G1Γ’ΒΒS 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 G1Γ’ΒΒS 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 G1Γ’ΒΒS phase cell cycle transition in embryonic stem cells.
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