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Nat Struct Mol Biol. 2011 Mar;18(3):302-8. doi: 10.1038/nsmb.1986. Epub 2011 Feb 6.

LIN-28 co-transcriptionally binds primary let-7 to regulate miRNA maturation in Caenorhabditis elegans.

Author information

1
Department of Biology, University of California, San Diego, La Jolla, CA, USA.

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.

PMID:
21297634
PMCID:
PMC3077891
DOI:
10.1038/nsmb.1986
[Indexed for MEDLINE]
Free PMC Article

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