Journal
NUCLEIC ACIDS RESEARCH
Volume 38, Issue 11, Pages 3780-3793Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq083
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Funding
- Cancer Research UK [C13474, C14303]
- Wellcome Trust (UK)
- National Institutes of Health [NS064273]
- EPSRC (UK)
- Hutchison Whampoa Limited
- Cancer Research UK [19556, 11832] Funding Source: researchfish
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miR-124 is a highly conserved microRNA (miRNA) whose in vivo function is poorly understood. Here, we identify miR-124 targets based on the analysis of the first mir-124 mutant in any organism. We find that miR-124 is expressed in many sensory neurons in Caenorhabditis elegans and onset of expression coincides with neuronal morphogenesis. We analyzed the transcriptome of miR-124 expressing and nonexpressing cells from wild-type and mir-124 mutants. We observe that many targets are co-expressed with and actively repressed by miR-124. These targets are expressed at reduced relative levels in sensory neurons compared to the rest of the animal. Our data from mir-124 mutant animals show that this effect is due to a large extent to the activity of miR-124. Genes with nonconserved target sites show reduced absolute expression levels in sensory neurons. In contrast, absolute expression levels of genes with conserved sites are comparable to control genes, suggesting a tuning function for many of these targets. We conclude that miR-124 contributes to defining cell-type-specific gene activity by repressing a diverse set of co-expressed genes.
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