Multiple in vivo biological processes are mediated by functionally redundant activities of Drosophila mir-279 and mir-996 Journal Article
| Authors: | Sun, K.; Jee, D.; de Navas, L. F.; Duan, H.; Lai, E. C. |
| Article Title: | Multiple in vivo biological processes are mediated by functionally redundant activities of Drosophila mir-279 and mir-996 |
| Abstract: | While most miRNA knockouts exhibit only subtle defects, a handful of miRNAs are profoundly required for development or physiology. A particularly compelling locus is Drosophila mir-279, which was reported as essential to restrict the emergence of CO<inf>2</inf>-sensing neurons, to maintain circadian rhythm, and to regulate ovarian border cells. The mir-996 locus is located near mir-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 the mir-279 and mir-996 hairpins, and cursory analysis suggested that miR-996 was dispensable. However, discrepancies in the strength of individual mir-279 deletion alleles led us to uncover that all extant mir-279 mutants 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 deletion background, allowing a pure assessment of miR-279 and miR-996 requirements. Surprisingly, detailed analyses of viability, olfactory neuron specification, and circadian rhythm indicate that miR-279 is completely dispensable. Instead, an endogenous supply of either mir-279 or mir-996 suffices for normal development and behavior. Sensor tests of nine key miR-279/996 targets showed their similar regulatory capacities, although transgenic gain-of-function experiments indicate partially distinct activities of these miRNAs that may underlie that co-maintenance in genomes. Altogether, we elucidate the unexpected genetics of this critical miRNA operon, and provide a foundation for their further study. More importantly, these studies demonstrate that multiple, vital, loss-of-function phenotypes can be rescued by endogenous expression of divergent seed family members, highlighting the importance of this miRNA region for in vivo function. © 2015 Sun et al. |
| Keywords: | controlled study; unclassified drug; gene deletion; nonhuman; phenotype; cell viability; microrna; gene expression; gene locus; gene frequency; drosophila; in vivo study; homozygosity; transgene; rna sequence; operon; circadian rhythm; microrna 279; olfactory nerve; phylogenomics; article; microrna 996 |
| Journal Title: | PLoS Genetics |
| Volume: | 11 |
| Issue: | 6 |
| ISSN: | 1553-7390 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-06-04 |
| Start Page: | e1005245 |
| Language: | English |
| DOI: | 10.1371/journal.pgen.1005245 |
| PROVIDER: | scopus |
| PMCID: | PMC4456407 |
| PUBMED: | 26042831 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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