Program in Molecular Medicine
The sequence and roles in developmental progression of the microRNA let-7 are conserved. In general, transcription of the let-7 primary transcript (pri-let-7) occurs early in development, whereas processing of the mature let-7 microRNA arises during cellular differentiation. In Caenorhabditis elegans and other animals, the RNA-binding protein LIN-28 post-transcriptionally inhibits let-7 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 let-7 might influence the expression or activities of other microRNAs of the same seed family. Here, we show that pri-let-7 is trans-spliced to the SL1 splice leader downstream of the let-7 precursor stem-loop, which produces a short polyadenylated downstream mRNA, and that this trans-splicing event negatively impacts the biogenesis of mature let-7 microRNA in cis Moreover, this trans-spliced mRNA contains sequences that are complementary to multiple members of the let-7 seed family (let-7fam) and negatively regulates 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.
Caenorhabditis elegans, Developmental timing, Trans-splicing, let-7 family microRNAs, lin-28
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© 2019. Published by The Company of Biologists Ltd. Publisher PDF posted after 12 months as allowed by the publisher's policy at http://dev.biologists.org/content/rights-permissions.
DOI of Published Version
Development. 2019 Mar 4;146(5). pii: dev172031. doi: 10.1242/dev.172031.
Development (Cambridge, England)
Nelson C, Ambros VR. (2019). Trans-splicing of the C. elegans let-7 primary transcript developmentally regulates let-7 microRNA biogenesis and let-7 family microRNA activity. Open Access Articles. https://doi.org/10.1242/dev.172031. Retrieved from https://escholarship.umassmed.edu/oapubs/3783
Available for download on Wednesday, March 04, 2020