Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation

Cell. 2005 Aug 26;122(4):553-63. doi: 10.1016/j.cell.2005.07.031.


MicroRNAs (miRNAs) are approximately 22 nucleotide RNAs that negatively regulate the expression of protein-coding genes. In a present model of miRNA function in animals, miRNAs that form imperfect duplexes with their targets inhibit protein expression without affecting mRNA levels. Here, we report that in C. elegans, regulation by the let-7 miRNA results in degradation of its lin-41 target mRNA, despite the fact that its 3'UTR regulatory sequences can only partially base-pair with the miRNA. Furthermore, lin-14 and lin-28 are targets of the lin-4 miRNA, and we show that the mRNA levels for these protein-coding genes significantly decrease in response to lin-4 expression. This study reveals that mRNAs containing partial miRNA complementary sites can be targeted for degradation in vivo, raising the possibility that regulation at the level of mRNA stability may be more common than previously appreciated for the miRNA pathway.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Gene Expression Regulation / genetics
  • Genes, Regulator / genetics
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA Interference / physiology
  • RNA Stability / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • LIN-14 protein, C elegans
  • LIN-28 protein, C elegans
  • LIN-41 protein, C elegans
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • let-7 microRNA, C elegans
  • lin-4 microRNA, C elegans