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• W2888314933 abstract "SUMMARY let-7 is a microRNA whose sequence and roles as a regulator of developmental progression are conserved throughout bilaterians. In most systems, transcription of the let-7 locus occurs relatively early in development, whilst processing of let-7 primary transcript into mature microRNA arises later and is associated with cellular differentiation. In C. elegans and other animals, the RNA binding protein LIN-28 post-transcriptionally inhibits let-7 biogenesis at early developmental stages. The mechanisms by which LIN-28 and other factors developmentally regulate let-7 biogenesis are not fully understood. Nor is it understood how the developmental regulation of let-7 might influence the expression or activities of other microRNAs of the same seed family. Here we show that in C. elegans , the primary let-7 transcript ( pri-let-7 ) is trans-spliced to SL1 splice leader at a position downstream of the let-7 precursor stem-loop, producing a short, polyadenylated downstream mRNA. The trans-splicing event negatively impacts the biogenesis of mature let-7 microRNA in cis , likely by destabilizing the upstream pri-let-7 fragment. Moreover, the trans-spliced downstream mRNA contains complimentary sequences to multiple members of the let-7 seed family ( let-7fam ), and thereby serves as a sponge to negatively regulate let-7fam function in trans . Thus, this study provides evidence for a mechanism by which splicing of a microRNA primary transcript can negatively regulate said microRNA in cis as well as other microRNAs in trans . HIGHLIGHTS The let-7 primary transcript is trans-spliced to produce an RNA that functions as a sponge that negatively regulates the let-7-family microRNAs. Trans-splicing of this RNA negatively impacts let-7 microRNA biogenesis. LIN-28 regulates this trans-splicing event" @default.
• W2888314933 created "2018-08-31" @default.
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• W2888314933 date "2018-08-24" @default.
• W2888314933 modified "2023-10-03" @default.
• W2888314933 title "Trans-splicing of the<i>C. elegans let-7</i>primary transcript developmentally regulates<i>let-7</i>microRNA biogenesis and<i>let-7</i>family microRNA activity" @default.
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• W2888314933 doi "https://doi.org/10.1101/400077" @default.
• W2888314933 hasPublicationYear "2018" @default.
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