Tissue-specific role of dTrmO in threonine decoding during Drosophila melanogaster development

Translation is an extremely fine-tuned process. Both speed and fidelity are required to sustain translational demand and protein homeostasis in cells, traits that depend on several elements, including transfer RNA (tRNA) modifications. Additionally, it has been demonstrated that proliferative and differentiated tissues display differential susceptibilities to deficiencies in certain tRNA modifications. By using the Gal4/UAS system we manipulated the expression levels of the Drosophila melanogaster orthologue of TrmO (dTrmO), a tRNA-methyltransferase that methylates t6A in position 37 of tRNAs decoding ACY codons, during development. Our results show that this protein is necessary for proper translation of ACT codons, and its function is differentially required in proliferative and non-proliferative tissues. Furthermore, we observed that reductions of dTrmO are detrimental for cell growth and proliferation, and muscle function due to impaired translation of Msp300, a nuclear membrane protein specific of muscle fibres. Strikingly, the translation-related phenotypes produced caused by decreased levels of dTrmO in the wing and eye-antenna imaginal disc, fat body, striated muscles, as well as overall organismal growth defects, can be rescued by overexpression of tRNA-Thr-AGT. Results point to the importance of dTrmO in translation of ACT codons and consequently in cell proliferation and growth of tissues, thus providing further insight about the active role of tRNA modifications in the context of eumetazoan development.