Diverse Endonucleolytic Cleavage Sites in the Mammalian Transcriptome Depend upon MicroRNAs, Drosha, and Additional Nucleases

Karginov, F. V., Cheloufi, S., Chong, M. M. W., Stark, A., Smith, A. D., Hannon, G. J. (June 2010) Diverse Endonucleolytic Cleavage Sites in the Mammalian Transcriptome Depend upon MicroRNAs, Drosha, and Additional Nucleases. Molecular Cell, 38 (6). pp. 781-788. ISSN 1097-2765

URL: http://www.ncbi.nlm.nih.gov/pubmed/20620951
DOI: 10.1016/j.molcel.2010.06.001

Abstract

The life span of a mammalian mRNA is determined, in part, by the binding of regulatory proteins and small RNA-guided complexes. The conserved endonuclease activity of Argonaute2 requires extensive complementarity between a small RNA and its target and is not used by animal microRNAs, which pair with their targets imperfectly. Here we investigate the endonucleolytic function of Ago2 and other nucleases by transcriptome-wide profiling of mRNA cleavage products retaining 5' phosphate groups in mouse embryonic stem cells (mESCs). We detect a prominent signature of Ago2-dependent cleavage events and validate several such targets. Unexpectedly, a broader class of Ago2-independent cleavage sites is also observed, indicating participation of additional nucleases in site-specific mRNA cleavage. Within this class, we identify a cohort of Drosha-dependent mRNA cleavage events that functionally regulate mRNA levels in mESCs, including one in the Dgcr8 mRNA. Together, these results highlight the underappreciated role of endonucleolytic cleavage in controlling mRNA fates in mammals.

Item Type: Paper
Uncontrolled Keywords: MESSENGER-RNA ENDORIBONUCLEASE IDENTIFICATION COMPLEX SMG6 SIRNAS DGCR8
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > RNA polymerase
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

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > siRNA
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Hannon lab
Depositing User: CSHL Librarian
Date: 25 June 2010
Date Deposited: 04 Oct 2011 14:27
Last Modified: 02 May 2013 19:32
PMCID: PMC2914474
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15446

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