Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-10

AUTHORS

John P. Hagan, Elena Piskounova, Richard I. Gregory

ABSTRACT

Lin28 and Lin28B, two developmentally regulated RNA-binding proteins and likely proto-oncogenes, selectively inhibit the maturation of let-7 family microRNAs (miRNAs) in embryonic stem cells and certain cancer cell lines. Moreover, let-7 precursors (pre-let-7) were previously found to be terminally uridylated in a Lin28-dependent fashion. Here we identify Zcchc11 (zinc finger, CCHC domain containing 11) as the 3' terminal uridylyl transferase (TUTase) responsible for Lin28-mediated pre-let-7 uridylation and subsequent blockade of let-7 processing in mouse embryonic stem cells. We demonstrate that Zcchc11 activity is UTP-dependent, selective for let-7 and recruited by Lin28. Furthermore, knockdown of either Zcchc11 or Lin28, or overexpression of a catalytically inactive TUTase, relieves the selective inhibition of let-7 processing and leads to the accumulation of mature let-7 miRNAs and repression of let-7 target reporter genes. Our results establish a role for Zcchc11-catalyzed pre-let-7 uridylation in the control of miRNA biogenesis. More... »

PAGES

1021-1025

References to SciGraph publications

  • 2009-06. Genetic variation in LIN28B is associated with the timing of puberty in NATURE GENETICS
  • 2009-06. Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche in NATURE GENETICS
  • 2009-07. Lin28 promotes transformation and is associated with advanced human malignancies in NATURE GENETICS
  • 2009-06. Meta-analysis of genome-wide association data identifies two loci influencing age at menarche in NATURE GENETICS
  • 2009-06. Loci at chromosomes 13, 19 and 20 influence age at natural menopause in NATURE GENETICS
  • 2009-06. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause in NATURE GENETICS
  • 2008-05. Identification of ten loci associated with height highlights new biological pathways in human growth in NATURE GENETICS
  • 2009-03. Many roads to maturity: microRNA biogenesis pathways and their regulation in NATURE CELL BIOLOGY
  • 2008-08. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment in NATURE CELL BIOLOGY
  • 2009-06. Decapping is preceded by 3′ uridylation in a novel pathway of bulk mRNA turnover in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2009-10. LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2006-04. Oncomirs — microRNAs with a role in cancer in NATURE REVIEWS CANCER
  • 2009-08. A role for Lin28 in primordial germ-cell development and germ-cell malignancy in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nsmb.1676

    DOI

    http://dx.doi.org/10.1038/nsmb.1676

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19713958


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