A dicer-independent miRNA biogenesis pathway that requires Ago catalysis View Full Text


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Article Info

DATE

2010-04-27

AUTHORS

Sihem Cheloufi, Camila O. Dos Santos, Mark M. W. Chong, Gregory J. Hannon

ABSTRACT

The nucleolytic activity of animal Argonaute proteins is deeply conserved, despite its having no obvious role in microRNA-directed gene regulation. In mice, Ago2 (also known as Eif2c2) is uniquely required for viability, and only this family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, we engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anaemia. Examination of microRNAs and their potential targets revealed a loss of miR-451, a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha (also known as Rnasen), its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic centre to generate an intermediate 3′ end, which is then further trimmed. Our findings link the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development. More... »

PAGES

584-589

References to SciGraph publications

  • 2004-11-07. Processing of primary microRNAs by the Microprocessor complex in NATURE
  • 2005-06-22. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing in NATURE
  • 2006-12-15. Slicer and the Argonautes in NATURE CHEMICAL BIOLOGY
  • 2008-01. Argonaute proteins: key players in RNA silencing in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2009-08-10. Essential role for Argonaute2 protein in mouse oogenesis in EPIGENETICS & CHROMATIN
  • 2001-07. Placental development: Lessons from mouse mutants in NATURE REVIEWS GENETICS
  • 2005-02-16. Identification of microRNAs of the herpesvirus family in NATURE METHODS
  • 2004-12-26. Synthetic shRNAs as potent RNAi triggers in NATURE BIOTECHNOLOGY
  • 2009-10-11. Structural insights into RNA processing by the human RISC-loading complex in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2009-02. Biogenesis of small RNAs in animals in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2008-08-27. Structure of the guide-strand-containing argonaute silencing complex in NATURE
  • 2003-09. The nuclear RNase III Drosha initiates microRNA processing in NATURE
  • 2008-04-10. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes in NATURE
  • 2005-12. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development in NATURE
  • 2008-01-06. Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta in NATURE GENETICS
  • 2008-04-10. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes in NATURE
  • 2003-11-16. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2005-03-30. Purified Argonaute2 and an siRNA form recombinant human RISC in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • Journal

    TITLE

    Nature

    ISSUE

    7298

    VOLUME

    465

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09092

    DOI

    http://dx.doi.org/10.1038/nature09092

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1018277529

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20424607


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