title: LIN-28 co-transcriptionally binds primary let-7 to regulate miRNA maturation in Caenorhabditis elegans.
abstract: The highly conserved let-7 microRNA (miRNA) regulates developmental pathways across animal phyla. Mis-expression of let-7 causes lethality in C. elegans and has been associated with several human diseases. We show that timing of let-7 expression in developing worms is under complex transcriptional and post-transcriptional control. Expression of let-7 primary transcripts oscillates during each larval stage, but precursor and mature let-7 miRNAs do not accumulate until later in development after LIN-28 protein has diminished. We demonstrate that LIN-28 binds endogenous primary let-7 transcripts co-transcriptionally. We further show that LIN-28 binds endogenous primary let-7 transcripts in the nuclear compartment of human ES cells, suggesting that this LIN-28 activity is conserved across species. We conclude that co-transcriptional interaction of LIN-28 with let-7 primary transcripts blocks Drosha processing and, thus, precocious expression of mature let-7 during early development.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Priscilla M
authors.initials: PM
authors.lastname: Van Wynsberghe
authors.forename: Zoya S
authors.initials: ZS
authors.lastname: Kai
authors.forename: Katlin B
authors.initials: KB
authors.lastname: Massirer
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Burton
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.forename: Amy E
authors.initials: AE
authors.lastname: Pasquinelli
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; C452195:LIN-28 protein, C elegans; D035683:MicroRNAs; D012097:Repressor Proteins