title: miR-9a minimizes the phenotypic impact of genomic diversity by buffering a transcription factor.
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.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Cassidy
authors.affiliation: Institute for Genomics and Systems Biology, Departments of Human Genetics and Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Aashish R
authors.initials: AR
authors.lastname: Jha
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Posadas
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Ritika
authors.initials: R
authors.lastname: Giri
authors.affiliation: Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Koen J T
authors.initials: KJ
authors.lastname: Venken
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jingran
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Statistics, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
authors.affiliation: Institute for Genomics and Systems Biology, Departments of Human Genetics and Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: r-carthew@northwestern.edu.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Carthew
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D049750:Genome, Insect; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C547291:MIRN9 microRNA, Drosophila; D035683:MicroRNAs; D009687:Nuclear Proteins; D014157:Transcription Factors; C413162:sens protein, Drosophila