Post-transcriptional regulation of gene expression is a crucial cellular property present in virtually all cells and cell types. Micro-RNAs (miRNAs) have been at the foremost of this type of regulation by specifically targeting the 3' untranslated region of target messenger RNAs that results in a negative effect on protein production. Here, we focused on the C. elegans homologue of the human tumor suppressor miRNA hs-
mir-31, namely the cel-
mir-269, and we found that it is expressed in two pair of neurons, the sensory neurons ASJ and the interneurons RIA. We used a knock-out (KO)
mir-269 mutant strain to test for aberrant behavioral phenotypes that could be associated with a role of this miRNA in these neurons. We found that
mir-269 KO animals had a delayed bacteria lawn leaving phenotype compared to wild-type animals when the pathogenic Pseudomonas aeruginosa strain PA14 was used as the food lawn. This defect was rescued by resupplying
mir-269 in ASJ neurons suggesting a specific role of
mir-269 in these sensory neurons in regulating the lawn leaving behavior. It has been previously shown that TGF-? signaling acts from ASJ neurons to regulate this behavior, and we found that
daf-7, the C. elegans homologue of the TGF-? ligand, is aberrantly expressed in the
mir-269 KO animals. We are currently working on testing a potential link between the
mir-269 and the TGF-? pathway in this behavioral example in order to understand more about the function of this miRNA in ASJ neurons. Meanwhile, the
mir-269 KO animals also exhibit an exaggerated head bending behavior, which is rescued by resupplying
mir-269 in RIA interneurons suggesting a separate role of this miRNA in the RIA neurons. To identify relevant
mir-269 targets in RIA, we sorted GFP-labelled RIA cell bodies from
mir-269 KO mutant and wild-type animals and compared their transcriptomes. We found differences in the expression level of components of the evolutionary conserved MCU-1 mitochondrial complex, the sole molecular machinery found to date to import cytoplasmic Ca++ into mitochondria. We are currently working on testing whether this misregulation could explain the head bending defects of the
mir-269 KO animals. Here, in this presentation, we will report our progress on these two distinct roles of the
mir-269 in ASJ and RIA with the intention to understand more about the role of a phylogenetically well-conserved miRNA in distinct neuronal functions.