Yang, J. S., Phillips, M. D., Betel, D., Mu, P., Ventura, A., Siepel, A. C., Chen, K. C., Lai, E. C. (February 2011) Widespread regulatory activity of vertebrate microRNA* species. Rna, 17 (2). pp. 312-26. ISSN 1355-8382
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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: | February 2011 |
| Date Deposited: | 12 Jan 2015 16:34 |
| Last Modified: | 12 Jan 2015 16:34 |
| PMCID: | PMC3022280 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31115 |
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