MiR-9a minimizes the phenotypic impact of genomic diversity by buffering a transcription factor

Justin J. Cassidy, Aashish R. Jha, Diana M. Posadas, Ritika Giri, Koen J.T. Venken, Jingran Ji, Hongmei Jiang, Hugo J. Bellen, Kevin P. White, Richard W. Carthew

Research output: Contribution to journalArticle

Abstract

Gene expression has to withstand stochastic, environmental, and genomic perturbations. For example, in the latter case, 0.5%-1% of the human genome is typically variable between any two unrelated individuals. Such diversity might create problematic variability in the activity of gene regulatory networks and, ultimately, in cell behaviors. Using multigenerational selection experiments, we find that for the Drosophila proneural network, the effect of genomic diversity is dampened by miR-9a-mediated regulation of senseless expression. Reducing miR-9a regulation of the Senseless transcription factor frees the genomic landscape to exert greater phenotypic influence. Whole-genome sequencing identified genomic loci that potentially exert such effects. A larger set of sequence variants, including variants within proneural network genes, exhibits these characteristics when miR-9a concentration is reduced. These findings reveal that microRNA-target interactions may be a key mechanism by which the impact of genomic diversity on cell behavior is dampened.

Original languageEnglish (US)
Pages (from-to)1556-1567
Number of pages12
JournalCell
Volume155
Issue number7
DOIs
StatePublished - Dec 19 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Cassidy, J. J., Jha, A. R., Posadas, D. M., Giri, R., Venken, K. J. T., Ji, J., Jiang, H., Bellen, H. J., White, K. P., & Carthew, R. W. (2013). MiR-9a minimizes the phenotypic impact of genomic diversity by buffering a transcription factor. Cell, 155(7), 1556-1567. https://doi.org/10.1016/j.cell.2013.10.057