PT  - JOURNAL ARTICLE
AU  - Bridget Donnelly
AU  - Bing Yang
AU  - Chen-Yu Liu
AU  - Katherine McJunkin
TI  - The developmentally-timed decay of an essential microRNA family is seed sequence-dependent
AID  - 10.1101/2021.11.19.469346
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.11.19.469346
4099  - http://biorxiv.org/content/early/2021/11/20/2021.11.19.469346.short
4100  - http://biorxiv.org/content/early/2021/11/20/2021.11.19.469346.full
AB  - MicroRNA (miRNA) abundance is tightly controlled by regulation of biogenesis and decay. Here we show that the mir-35 miRNA family undergoes regulated decay at the transition from embryonic to larval development in C. elegans. The seed sequence of the miRNA is necessary and 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.Competing Interest StatementThe authors have declared no competing interest.