Systematic Study of Drosophila MicroRNA Functions Using a Collection of Targeted Knockout Mutations

• Eighty new microRNA mutants, removing 104 miRNAs, are reported
• The complete miRNA mutant collection is composed of 95 mutants, removing 130 miRNAs
• These mutants account for >99% of Drosophila miRNA sequence reads
• At the 99% confidence level, >80% of the mutants produced an observable phenotype

SummaryMicroRNAs are abundant in animal genomes, yet little is known about their functions in vivo. Here, we report the production of 80 new Drosophila miRNA mutants by targeted homologous recombination. These mutants remove 104 miRNAs. Together with 15 previously reported mutants, this collection includes 95 mutants deleting 130 miRNAs. Collectively, these genes produce over 99% of all Drosophila miRNAs, measured by miRNA sequence reads. We present a survey of developmental and adult miRNA phenotypes. Over 80% of the mutants showed at least one phenotype using a p < 0.01 significance threshold. We observed a significant correlation between miRNA abundance and phenotypes related to survival and lifespan, but not to most other phenotypes. miRNA cluster mutants were no more likely than single miRNA mutants to produce significant phenotypes. This mutant collection will provide a resource for future analysis of the biological roles of Drosophila miRNAs.