LIN-28 Co-Transcriptionally Binds Primary let-7 to Regulate miRNA Maturation in Caenorhabditis Elegans

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Line
  • Gene Expression Regulation, Developmental*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic

Substances

  • Caenorhabditis elegans Proteins
  • LIN-28 protein, C elegans
  • MicroRNAs
  • Repressor Proteins