<i>
let-7</i> is a microRNA whose sequence and roles in developmental progression are conserved Generally, transcription of <i>
let-7</i> primary transcript (<i>pri-let-</i>7) occurs early in development, whilst processing of the mature <i>
let-7</i> microRNA arises during cellular differentiation. In <i>C. elegans</i> and other animals, the RNA binding protein LIN-28 post-transcriptionally inhibits <i>
let-7</i> 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 <i>
let-7</i> might influence the expression or activities of other microRNAs of the same seed family. Here we show that <i>pri-
let-7</i> is trans-spliced to the SL1 splice leader downstream of the <i>
let-7</i> precursor stem-loop, producing a short, polyadenylated downstream mRNA, and that this trans-splicing event negatively impacts the biogenesis of mature <i>
let-7</i> microRNA in <i>cis.</i> Moreover, this trans-spliced mRNA contains sequences complementary to multiple the <i>
let-7</i> seed family (<i>
let-7fam</i>) and negatively regulates <i>
let-7fam</i> function in <i>trans</i> Thus, this study provides evidence for a mechanism by which splicing of a microRNA primary transcript can negatively regulate said microRNA in <i>cis</i> as well as other microRNAs in <i>trans</i>.