An alternative mode of microRNA target recognition

Chi, S. W., Hannon, G. J., Darnell, R. B. (2012) An alternative mode of microRNA target recognition. Nature Structural and Molecular Biology, 19 (3). pp. 321-327. ISSN 15459993 (ISSN)

Abstract

MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ∼50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites. © 2012 Nature America, Inc. All rights reserved.

Item Type:	Paper
Uncontrolled Keywords:	argonaute protein microRNA mir 124 unclassified drug animal tissue article binding site brain controlled study human human cell molecular recognition mouse nonhuman priority journal protein binding protein interaction Base Pairing Binding Sites HeLa Cells Humans MicroRNAs Models, Genetic
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics 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
CSHL Authors:	Chi, Sung Wook Hannon, Gregory J.
Communities:	CSHL Cancer Center Shared Resources > Bioinformatics Service CSHL Cancer Center Shared Resources > DNA Sequencing Service CSHL labs > Hannon lab CSHL Cancer Center Program > Cancer Genetics
Depositing User:	Matt Covey
Date:	2012
Date Deposited:	09 Jan 2013 16:37
Last Modified:	13 Oct 2015 19:54
PMCID:	PMC3541676
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26421

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