Trans-splicing of the primary transcript developmentally regulates microRNA biogenesis and family microRNA activity.

The sequence and roles in developmental progression of the microRNA are conserved. In general, transcription of the primary transcript (7) occurs early in development, whereas processing of the mature microRNA arises during cellular differentiation. In and other animals, the RNA-binding protein LIN-28 post-transcriptionally inhibits biogenesis at early developmental stages, but the mechanisms by which LIN-28 does this are not fully understood. Nor is it understood how the developmental regulation of might influence the expression or activities of other microRNAs of the same seed family. Here, we show that is trans-spliced to the SL1 splice leader downstream of the precursor stem-loop, which produces a short polyadenylated downstream mRNA, and that this trans-splicing event negatively impacts the biogenesis of mature microRNA in Moreover, this trans-spliced mRNA contains sequences that are complementary to multiple members of the seed family () and negatively regulates function in Thus, this study provides evidence for a mechanism by which splicing of a microRNA primary transcript can negatively regulate said microRNA in as well as other microRNAs in .