TY  - JOUR
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
Y1  - 2015/11/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1680 
EP  - 1691 
DO  - 10.1101/gr.183160.114 
VL  - 25 
IS  - 11 
UR  - http://genome.cshlp.org/content/25/11/1680.abstract 
N2  - 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. 
ER  -