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.
Yekta
Soraya
S
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Shih
I-Hung
IH
Bartel
David P
DP
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation; D005801:Genes, Homeobox; D017930:Genes, Reporter; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
D020413:3' Untranslated Regions; C115962:HOXA7 protein, human; C490669:HOXB8 protein, human; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; C492047:Hoxa7 protein, mouse; C095822:Hoxb8 protein, mouse; C489816:Hoxc8 protein, mouse; C489576:Hoxd8 protein, mouse; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C075279:HOXD8 protein, human