• Priscilla M Van Wynsberghe, Zoya S Kai, Katlin B Massirer, Victoria H Burton, Gene W Yeo, and Amy E Pasquinelli.
• Department of Biology, University of California, San Diego, La Jolla, CA, USA.
• Nat. Struct. Mol. Biol. 2011 Mar 1; 18 (3): 302-8.

AbstractThe 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.

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