Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs.

Show simple item record Martin, Hilary C en Wani, Shivangi en Steptoe, Anita L en Krishnan, Keerthana en Nones, Katia en Nourbakhsh, Ehsan en Vlassov, Alexander en Grimmond, Sean M en Cloonan, Nicole en 2018-10-19T01:12:05Z en 2014-01 en
dc.identifier.citation Genome Biology 15(3):22 pages 14 Mar 2014 en
dc.identifier.issn 1474-7596 en
dc.identifier.uri en
dc.description.abstract BACKGROUND: MicroRNAs (miRNAs) bind to mRNAs and target them for translational inhibition or transcriptional degradation. It is thought that most miRNA-mRNA interactions involve the seed region at the 5' end of the miRNA. The importance of seed sites is supported by experimental evidence, although there is growing interest in interactions mediated by the central region of the miRNA, termed centered sites. To investigate the prevalence of these interactions, we apply a biotin pull-down method to determine the direct targets of ten human miRNAs, including four isomiRs that share centered sites, but not seeds, with their canonical partner miRNAs. RESULTS: We confirm that miRNAs and their isomiRs can interact with hundreds of mRNAs, and that imperfect centered sites are common mediators of miRNA-mRNA interactions. We experimentally demonstrate that these sites can repress mRNA activity, typically through translational repression, and are enriched in regions of the transcriptome bound by AGO. Finally, we show that the identification of imperfect centered sites is unlikely to be an artifact of our protocol caused by the biotinylation of the miRNA. However, the fact that there was a slight bias against seed sites in our protocol may have inflated the apparent prevalence of centered site-mediated interactions. CONCLUSIONS: Our results suggest that centered site-mediated interactions are much more frequent than previously thought. This may explain the evolutionary conservation of the central region of miRNAs, and has significant implications for decoding miRNA-regulated genetic networks, and for predicting the functional effect of variants that do not alter protein sequence. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Genome biology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.subject Humans en
dc.subject MicroRNAs en
dc.subject RNA, Messenger en
dc.subject RNA Processing, Post-Transcriptional en
dc.subject Binding Sites en
dc.subject Genome, Human en
dc.subject HEK293 Cells en
dc.title Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs. en
dc.type Journal Article en
dc.identifier.doi 10.1186/gb-2014-15-3-r51 en
pubs.issue 3 en
pubs.begin-page R51 en
pubs.volume 15 en
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 24629056 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 618268 en Science en Biological Sciences en
dc.identifier.eissn 1474-760X en
pubs.record-created-at-source-date 2014-08-22 en
pubs.dimensions-id 24629056 en

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