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MicroRNA-directed cleavage of HOXB8 mRNA.

MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs, some of which are known to play important regulatory roles in animals by targeting the messages of protein-coding genes for translational repression. We find that miR-196, a miRNA encoded at three paralogous locations in the A, B, and C mammalian HOX clusters, has extensive, evolutionarily conserved complementarity to messages of HOXB8, HOXC8, and HOXD8. RNA fragments diagnostic of miR-196-directed cleavage of HOXB8 were detected in mouse embryos. Cell culture experiments demonstrated down-regulation of HOXB8, HOXC8, HOXD8, and HOXA7 and supported the cleavage mechanism for miR-196-directed repression of HOXB8. These results point to a miRNA-mediated mechanism for the posttranscriptional restriction of HOX gene expression during vertebrate development and demonstrate that metazoan miRNAs can repress expression of their natural targets through mRNA cleavage in addition to inhibiting productive translation.

Pubmed ID: 15105502

Authors

  • Yekta S
  • Shih IH
  • Bartel DP

Journal

Science (New York, N.Y.)

Publication Data

April 23, 2004

Associated Grants

None

Mesh Terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Down-Regulation
  • Genes, Homeobox
  • Genes, Reporter
  • HeLa Cells
  • Homeodomain Proteins
  • Humans
  • Mice
  • MicroRNAs
  • Molecular Sequence Data
  • Neoplasm Proteins
  • RNA, Messenger
  • Sequence Alignment
  • Transcription Factors
  • Transfection