microRNAs are essential for development. However, in C. elegans, the individual functions of most microRNAs remain largely unknown. We previously identified phenotypes associated with the loss of individual microRNAs in genetically sensitized backgrounds, including loss of
alg-1 activity1. Among these phenotypes, we found that loss of
mir-51 family members suppresses phenotypes observed in
alg-1 mutant worms.
alg-1 mutants display developmental timing defects that are similar to
let-7 family mutants. We therefore examined genetic interactions between members of the
mir-51 family and
let-7 family. We found that loss of
mir-51 family members suppressed the developmental timing defects of
let-7 family mutants. Further genetic analysis with other developmental timing genes suggests that the
mir-51 family functions upstream of
hbl-1. In order to identify direct targets of the
mir-51 family whose up-regulation results in suppression of
let-7 family mutant phenotypes, we used RNAi to knockdown predicted miR-51 family targets. Since we found that
hbl-1, a microRNA target, was better regulated in the absence of
mir-51 family members, we examined the effect of loss of
mir-51 family members in other microRNA-mediated developmental pathways. We found that
mir-51 family members function antagonistically to other microRNAs, including
lsy-6 and
mir-240 mir-786. Our analysis identifies a post-embryonic function for this family of microRNAs in the developmental timing pathway in addition to its function during embryogenesis2,3. This analysis also suggests a broader role for the
mir-51 family in microRNA-mediated developmental pathways.
1.Brenner, J. L., Jasiewicz, K. L., Fahley, A. F., Kemp, B. J. & Abbott, A. L. Loss of Individual MicroRNAs Causes Mutant Phenotypes in Sensitized Genetic Backgrounds in C. elegans. Current biology : CB 20, 1321-1325 (2010).
2.Alvarez-Saavedra, E. & Horvitz, H. R. Many families of C. elegans microRNAs are not essential for development or viability. Current biology : CB 20, 367-373 (2010).
3.Shaw, W. R., Armisen, J., Lehrbach, N. J. & Miska, E. A. The conserved miR-51 microRNA family is redundantly required for embryonic development and pharynx attachment in Caenorhabditis elegans. Genetics 185, 897-905 (2010).