Widespread regulatory activity of vertebrate microRNA* species

Yang, J. S., Phillips, M. D., Betel, D., Mu, P., Ventura, A., Siepel, A. C., Chen, K. C., Lai, E. C. (2011) Widespread regulatory activity of vertebrate microRNA* species. Rna, 17 (2). pp. 312-26. ISSN 1355-8382

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URL: http://www.ncbi.nlm.nih.gov/pubmed/21177881
DOI: 10.1261/rna.2537911

Abstract

An obligate intermediate during microRNA (miRNA) biogenesis is an ~22-nucleotide RNA duplex, from which the mature miRNA is preferentially incorporated into a silencing complex. Its partner miRNA* species is generally regarded as a passenger RNA, whose regulatory capacity has not been systematically examined in vertebrates. Our bioinformatic analyses demonstrate that a substantial fraction of miRNA* species are stringently conserved over vertebrate evolution, collectively exhibit greatest conservation in their seed regions, and define complementary motifs whose conservation across vertebrate 3'-UTR evolution is statistically significant. Functional tests of 22 miRNA expression constructs revealed that a majority could repress both miRNA and miRNA* perfect match reporters, and the ratio of miRNA:miRNA* sensor repression was correlated with the endogenous ratio of miRNA:miRNA* reads. Analysis of microarray data provided transcriptome-wide evidence for the regulation of seed-matched targets for both mature and star strand species of several miRNAs relevant to oncogenesis, including mir-17, mir-34a, and mir-19. Finally, 3'-UTR sensor assays and mutagenesis tests confirmed direct repression of five miR-19* targets via star seed sites. Overall, our data demonstrate that miRNA* species have demonstrable impact on vertebrate regulatory networks and should be taken into account in studies of miRNA functions and their contribution to disease states.

Item Type: Paper
Uncontrolled Keywords: 3' Untranslated Regions/genetics Animals Base Sequence Humans MicroRNAs/*genetics Molecular Sequence Data Oligonucleotide Array Sequence Analysis Sequence Alignment Species Specificity Vertebrates/genetics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA regulation
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:
Communities: CSHL labs > Siepel lab
Depositing User: Matt Covey
Date Deposited: 12 Jan 2015 16:34
Last Modified: 12 Jan 2015 16:34
PMCID: PMC3022280
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31115

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