MicroRNA-Directed Cleavage of HOXB8 mRNA
Abstract
MicroRNAs (miRNAs) are endogenous ∼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.
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MiR-196 is unusual among known animal miRNAs for its near-perfect complementarity to its HOXB8 target site and for inducing cleavage of the HOXB8 mRNA rather than inhibiting translation.
“MiR-196 is unusual among known animal miRNAs for its near-perfect complementarity to its HOXB8 target site and for inducing cleavage of the HOXB8 mRNA rather than inhibiting translation (Yekta et al. 2004).”
From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Yekta et al. 2004
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- Authors
- Yekta, S., Shih, I.-H., & Bartel, D. P.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- ORCID
- Bartel, David P.
- Venue
- Science
- Published
- 2004-04-23
- Volume
- 304
- Issue
- 5670
- Pages
- 594-596
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2042673698
- Cited by
- 1,702
- References
- 0
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 24 · 2023: 28 · 2022: 25 · 2021: 52 · 2020: 44 · 2019: 55 · 2018: 58 · 2017: 66 · 2016: 51 · 2015: 69 · 2014: 90 · 2013: 105 · 2012: 115
- FWCI
- 51.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- microRNA, miR-196, Hoxb8, mRNA cleavage, post-transcriptional regulation, protein synthesis inhibition, Hox genes, mouse embryo, gene downregulation, vertebrate development
- MeSH terms
- Animals, Base Sequence, Genes, Homeobox, HeLa Cells, Humans, Molecular Sequence Data, Neoplasm Proteins, RNA, Messenger, Transcription Factors, Transfection, Down-Regulation, Sequence Alignment, Genes, Reporter, Homeodomain Proteins, 3' Untranslated Regions, MicroRNAs, Mice
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