RESEARCH ARTICLE Multiple In Vivo Biological Processes Are Mediated by Functionally Redundant Activities of Drosophila mir-279 andmir-996

While most miRNA knockouts exhibit only subtle defects, a handful of miRNAs are pro-foundly required for development or physiology. A particularly compelling locus is Drosophi-la mir-279, which was reported as essential to restrict the emergence of CO2-sensing neurons, to maintain circadian rhythm, and to regulate ovarian border cells. Themir-996 locus is located nearmir-279 and bears a similar seed, but they otherwise have distinct, conserved, non-seed sequences, suggesting their evolutionary maintenance for separate functions. We generated single and double deletion mutants of themir-279 andmir-996 hairpins, and cursory analysis suggested that miR-996 was dispensable. However, discrep-ancies in the strength of individualmir-279 deletion alleles led us to uncover that all extant mir-279mutants are deficient for mature miR-996, even though they retain its genomic locus. We therefore engineered a panel of genomic rescue transgenes into the double dele-tion background, allowing a pure assessment of miR-279 and miR-996 requirements. Sur-prisingly, detailed analyses of viability, olfactory neuron specification, and circadian rhythm indicate that miR-279 is completely dispensable. Instead, an endogenous supply of eithe