Vinay K Mayya, Mathieu N Flamand, Alice M Lambert, Seyed Mehdi Jafarnejad, James A Wohlschlegel, Nahum Sonenberg, and Thomas F Duchaine
Nucleic Acids Research, gkab162, doi:10.1093/nar/gkab162
Ever since the discovery of microRNAs in C. elegans, their precise mechanism of action and the breadth of their biological impact has remained a matter of debate. Using a combination of unbiased proteomics, cell-free assays, genetics, and CRISPR/Cas9-based methods the authors identify the first direct effector of microRNA-directed translational repression in C. elegans, the novel GYF-domain protein GYF-1 and its partner IFE-4, and survey their physiological functions across several signature microRNA cascades using precisely engineered alleles and loci. The results provide a clear view of the importance of microRNA-directed translational repression in some, but not all microRNA cascades in C. elegans development, and unveil the surprising systems’ flexibility among microRNA’s silencing mechanisms. This discovery is of particularly high impact in that it provides exceptional new insight into the biological purposes of microRNAs in developmental and physiological contexts.