Caenorhabditis elegans organizmasında trehalozun mirna ilişkili embriyonik gelişimdeki olası rolü

MicroRNAs (miRNAs) are an essential class of non-coding RNAs that post-transcriptionally repress mRNAs. miRNAs were first identified in Caenorhabditis elegans as important regulators of developmental timing. Since then, miRNAs have been shown roles in nearly all biological processes. Most important process in which miRNAs take place is developmental processes. Caenorhabditis elegans is a terrestrial nematode and a widely used model organism for studying biological processes development and aging related to miRNA gene function. A conditional allele of miRNA biogenesis gene, pash-1 allows to regulate miRNA production by simply changing the growth temperature in worms. Grown at 15°C, pash-1 mutant animals have normal miRNA levels and shifting the temperature to 25°C ceases miRNA production and leads to rapid ageing, motility defects and embryonic lethality. In our efforts to understand the roles of miRNAs in ageing, we observed a highly interesting phenomenon with one of the chemicals under investigation. Growing the pash-1 mutant animals in the presence of trehalose rescued the embryonic lethality phenotype at 25°C. Trehalose is a non-reducing disaccharide [α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside] of glucose. Trehalose is present in a variety of organisms such as bacteria, yeasts, fungi, insects, invertebrates and plants. C. elegans accumulate detectable amount of trehalose in embryonic and dauer stages of C. elegans. However, the importance of trehalose for developmental processes or its physiology remains to be explored in this model organism. In this study, we focused on the effects of trehalose on the embryogenesis of C. elegans that lacks miRNA biogenesis. While trehalose rescued the embryonic lethality of pash-1(mj100) and mir-35 loss of function mutants, it failed to rescue embryonic lethality of miRNA independent temperature-sensitive embryonic lethal mutants, indicating the specificity of the trehalose effect. Trehalose can function as a chemical chaperone, autophagy inducer, a metabolite and a signaling molecule. In order to understand how trehalose alleviates embryonic lethality phenotype, we tested various chemicals in parallel to trehalose. We showed that autophagy inducer rapamycin does not have the same effect on the embryonic lethality. However, two chemical chaperones proline and serine have similar effects on embryonic lethality as trehalose does. Further efforts will be required to understand how trehalose affects miRNA function in embryogenesis, however, as this is the first time a chemical has been shown to rescue miRNA-related defect, this will have great impact on efforts in developing therapies in various diseases resulting from the loss of miRNA gene function. Key words: Trehalose, C. elegans, miRNAs, embryonic lethality, pash-1(mj100), mir-35(ndf50), mir-52(ndf58)