RT Journal
A1 Subasic, Deni
A1 Brümmer, Anneke
A1 Wu, Yibo
A1 Pinto, Sérgio Morgado
A1 Imig, Jochen
A1 Keller, Martin
A1 Jovanovic, Marko
A1 Lightfoot, Helen Louise
A1 Nasso, Sara
A1 Goetze, Sandra
A1 Brunner, Erich
A1 Hall, Jonathan
A1 Aebersold, Ruedi
A1 Zavolan, Mihaela
A1 Hengartner, Michael O.
T1 Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans
JF Genome Research 
JO Genome Research 
YR 2015 
FD November 01 
VO 25 
IS 11 
SP 1680 
OP 1691 
DO 10.1101/gr.183160.114 
UL http://genome.cshlp.org/content/25/11/1680.abstract 
AB 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 Caenorhabditis elegans miR-58 miRNA family, composed primarily of the four highly abundant members miR-58.1, 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 up-regulation 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-58.1 differ in a single nucleotide, predicted canonical miR-80 targets were efficiently up-regulated in the mir-58.1 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.