Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans

Subasic, Deni and Brümmer, Anneke and Wu, Yibo and Pinto, Sérgio Morgado and Imig, Jochen and Keller, Martin and Jovanovic, Marko and Lightfoot, Helen Louise and Nasso, Sara and Götze, Sandra and Brunner, Erich and Hall, Jonathan and Aebersold, Ruedi and Zavolan, Mihaela and Hengartner, Michael. (2015) Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans. Genome research, 25 (11). pp. 1680-1691.

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Official URL: http://edoc.unibas.ch/39444/

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In animals, microRNAs frequently form families with related sequences. The functional relevance of miRNA families and the relative contribution of family members to target repression have remained, however, largely unexplored. Here, we used the C. elegans miR-58 miRNA family, comprised primarily of the four highly abundant members miR-58, miR-80, miR-81 and miR-82, as a model to investigate the redundancy of miRNA family members and their impact on target expression in an in vivo setting. We found that miR-58 family members repress largely overlapping sets of targets in a predominantly additive fashion. Progressive deletions of miR-58 family members lead to cumulative upregulation of target protein and RNA levels. Phenotypic defects could only be observed in the family quadruple mutant, which also showed the strongest change in target protein levels. Interestingly, although the seed sequences of miR-80 and miR-58 differ in one nucleotide, predicted canonical miR-80 targets were efficiently upregulated in the mir-58 single mutant, indicating functional redundancy of distinct members of this miRNA family. At the aggregate level, target binding leads mainly to mRNA degradation, although we also observed some degree of translational inhibition, particularly in the single miR-58 family mutants. These results provide a framework for understanding how miRNA family members interact to regulate target mRNAs.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Brümmer, Anneke
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cold Spring Harbor Laboratory Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Jun 2016 10:59
Deposited On:04 May 2016 09:20

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