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MicroRNAs in the Hox network: an apparent link to posterior prevalence

Nature Reviews Genetics volume 9, pages 789–796 (2008)Cite this article

Key Points

  • Within Hox gene clusters are loci that encode microRNAs (miRNAs). These include: miR-10, found throughout Bilateria; miR-196, found in vertebrates; and miR-iab4, found in insects.

  • Hox miRNAs preferentially target the mRNA of Hox transcription factors, with a strong propensity to target those from loci situated on the 3′ side of each Hox miRNA locus.

  • These targeting preferences suggest that Hox miRNAs help repress more anterior programmes, thereby reinforcing posterior prevalence, which is the hierarchical control of posterior over anterior Hox gene function.

Abstract

Homeobox (Hox) transcription factors confer anterior–posterior (AP) axial coordinates to vertebrate embryos. Hox genes are found in clusters that also contain genes for microRNAs (miRNAs). Our analysis of predicted miRNA targets indicates that Hox cluster-embedded miRNAs preferentially target Hox mRNAs. Moreover, the presumed Hox target genes are predominantly situated on the 3′ side of each Hox miRNA locus. These results suggest that Hox miRNAs help repress more anterior programmes, thereby reinforcing posterior prevalence, which is the hierarchical dominance of posterior over anterior Hox gene function that is observed in bilaterians. In this way, miRNA-mediated regulation seems to recapitulate interactions at other levels of gene expression, some more ancestral, within a network under stabilizing selection.

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Figure 1: Predicted repression of Hox genes by Hox microRNAs.

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Acknowledgements

We thank laboratory members and collegues for helpful discussions. Supported by grants from the National Institutes of Health.

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Soraya Yekta & David P. Bartel

  2. and Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Soraya Yekta & David P. Bartel

  3. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, 02115, Massachusetts, USA

    Clifford J. Tabin

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  1. Soraya Yekta
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Correspondence to David P. Bartel.

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FURTHER INFORMATION

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The Tabin laboratory

MicroRNA target predictions

RefSeq

Glossary

Bilateria

Members of the animal clade that have bilateral symmetry — the property of having two similar sides, with definite upper and lower surfaces, and anterior and posterior ends. Bilaterians include chordates, arthropods, nematodes, annelids and molluscs, among other groups.

Non-synonymous mutation

A change in nucleotide sequence that alters the encoded amino acid.

Paralogous

The homology between two genomic segments in the same organism that arose from a duplication event.

Neofunctionalization

The process whereby a pair of duplicated genes becomes permanently preserved as one copy acquires mutations, conferring a new function.

Rhombomere

Each of seven neuroepithelial segments found in the embryonic hindbrain that adopt distinct molecular and cellular properties, restrictions in cell mixing, and ordered domains of gene expression.

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Yekta, S., Tabin, C. & Bartel, D. MicroRNAs in the Hox network: an apparent link to posterior prevalence. Nat Rev Genet 9, 789–796 (2008). https://doi.org/10.1038/nrg2400

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