MYC-REGULATED MIRNAS MODULATE P53 EXPRESSION AND IMPACT ANIMAL SURVIVAL UNDER NUTRIENT DEPRIVATION

SÁNCHEZ, JUAN ANDRÉS; GERVE PAULA; ANDRES DEKANTY; INGARAMO, MARÍA CLARA

Congreso; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2022

MicroRNAs (miRNAs), are endogenous small non-coding RNAs that mediate post-transcriptional regulation of gene expression.miRNAs exert diverse functions including the regulation of cell growth, proliferation and apoptosis, and the deregulation of manyof them has been associated with cancer. In the last decade, individual miRNAs have been associated with developmental andtissue-specific functions, however the transcription factors that regulate miRNA expression remain uncharacterized. Here we showthat the transcription factor Myc regulates miRNA expression and processing in Drosophila. Chromatin immunoprecipitation(ChIP) assays revealed that dMyc binds to DNA binding sites located at the loci of 56% of Drosophila miRNA coding genes andreduction of dMyc levels resulted in widespread downregulation of miRNAs gene expression. By using in vivo miRNA activitysensors we demonstrate that dMyc promotes miRNA-mediated silencing in different tissues, including the wing primordium andfat body. We also show that dMyc-dependent expression of miR-305 in the fat body modulates Dmp53 levels according to nutrientavailability, which has a profound impact on the ability of the organism to respond to nutrient stress. dMyc depletion in the fatbody resulted in extended survival to nutrient deprivation, which was reverted by coexpression of either miR-305 or a dominantnegative version of Dmp53. Our study reveals a previously unrecognized function of dMyc as an important regulator of miRNAexpression and processing, and suggests that Myc-dependent expression of specific miRNAs may have important tissue-specificfunctions