Widespread regulatory activity of vertebrate microRNA* species
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.
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Less abundant miR* strands were shown to repress mRNAs containing predicted miR* target sites in flies and mammals, suggesting that miR* strands are functional.
“Consistent with this idea, the less abundant miR* strands were shown repress mRNAs containing predicted miR* target sites in flies and mammals, suggesting that miR* strands are functional (Okamura et al., 2008; Yang et al., 2010).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Yang et al., 2010
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microRNA strand selection: Unwinding the rules
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- Authors
- Yang, J.-S., Phillips, M. D., Betel, D., Mu, P., Ventura, A., Siepel, A. C., Chen, K. C., & Lai, E. C.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-12-22
- Volume
- 17
- Issue
- 2
- Pages
- 312-326
- ISSN
- 1355-8382
- 1469-9001
- Cited by
- 304
- References
- 6
- Language
- en
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