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

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.

Pubmed ID: 21297634


  • Van Wynsberghe PM
  • Kai ZS
  • Massirer KB
  • Burton VH
  • Yeo GW
  • Pasquinelli AE


Nature structural & molecular biology

Publication Data

March 4, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: F32GM087004
  • Agency: NIGMS NIH HHS, Id: GM071654
  • Agency: NIGMS NIH HHS, Id: R01 GM071654
  • Agency: NIGMS NIH HHS, Id: R01 GM071654-07
  • Agency: NCI NIH HHS, Id: T32 CA009523

Mesh Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Cell Line
  • Gene Expression Regulation, Developmental
  • Humans
  • MicroRNAs
  • Protein Binding
  • Repressor Proteins
  • Transcription, Genetic