UMMS Affiliation

Program in Molecular Medicine

Publication Date

2019-03-04

Document Type

Article

Disciplines

Developmental Biology

Abstract

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.

Keywords

Caenorhabditis elegans, Developmental timing, Trans-splicing, let-7 family microRNAs, lin-28

Rights and Permissions

© 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

10.1242/dev.172031

Source

Development. 2019 Mar 4;146(5). pii: dev172031. doi: 10.1242/dev.172031.

Journal/Book/Conference Title

Development (Cambridge, England)

Related Resources

Link to article in PubMed

PubMed ID

30770392

Available for download on Wednesday, March 04, 2020

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