A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis

Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., Hannon, G. J. (2010) A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature, 465 (7298). 584-U76. ISSN 0028-0836

URL: http://www.ncbi.nlm.nih.gov/pubmed/20424607
DOI: 10.1038/nature09092

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 39 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.

Item Type: Paper
Uncontrolled Keywords: SMALL RNAS CRYSTAL-STRUCTURE ARGONAUTE FAMILY SILENCING COMPLEX INTERFERING RNAS MESSENGER-RNA MOUSE OOCYTES HUMAN RISC SLICER IDENTIFICATION
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA

organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Gene Targeting Service
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: CSHL Librarian
Date Deposited: 29 Sep 2011 14:20
Last Modified: 26 Dec 2014 20:56
PMCID: PMC2995450
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15383

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