Abstract MicroRNA (miRNA) abundance is tightly controlled by regulation of biogenesis and decay. Here we show that the mir-35 miRNA family undergoes selective decay at the transition from embryonic to larval development in C. elegans . The seed sequence of the miRNA is necessary and largely sufficient for this regulation. Sequences outside the seed (3’ end) regulate mir-35 abundance in the embryo but are not necessary for sharp decay at the transition to larval development. Enzymatic modifications of the miRNA 3’ end are neither prevalent nor correlated with changes in decay, suggesting that miRNA 3’ end display is not a core feature of this mechanism and further supporting a seed-driven decay model. Our findings demonstrate that seed sequence-specific decay can selectively and coherently regulate all redundant members of a miRNA seed family, a class of mechanism that has great biological and therapeutic potential for dynamic regulation of a miRNA family’s target repertoire.

The developmentally-timed decay of an essential microRNA family is seed sequence-dependent