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

Martin, Hilary C., Wani, Shivangi, Steptoe, Anita L., Krishnan, Keerthana, Nones, Katia, Nourbakhsh, Ehsan, Vlassov, Alexander, Grimmond, Sean M. and Cloonan, Nicole (2014) Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs. Genome Biology, 15 3: . doi:10.1186/gb-2014-15-3-r51


Author Martin, Hilary C.
Wani, Shivangi
Steptoe, Anita L.
Krishnan, Keerthana
Nones, Katia
Nourbakhsh, Ehsan
Vlassov, Alexander
Grimmond, Sean M.
Cloonan, Nicole
Title Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-760X
Publication date 2014-03-14
Year available 2014
Sub-type Article (original research)
DOI 10.1186/gb-2014-15-3-r51
Open Access Status DOI
Volume 15
Issue 3
Total pages 22
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # R51

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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