ena-STUDY-UNIVERSITY OF VIENNA-22-02-2019-09:50:58:009-152
Elucidation of purine-9 methylation in human nucleo-cytoplasmic tRNAs
The TRM10 family of methyltransferases is responsible for the methylation of position 9 in tRNAs in Archaea and Eukarya. The human genome encodes three enzymes of the family, of which only the mitochondrial form TRMT10C was previously characterized, whereas the function and the targets of TRMT10A and TRMT10B were not investigated so far. Here we show that TRMT10A and TRMT10B methylate a subset of nuclear-encoded tRNAs in human cells; the two enzymes have a completely distinct repertoire of targets, and show no functional redundancy. Remarkably, TRMT10A is guanosine-9 specific and methylates 11 distinct tRNAs, whilst TRMT10B is the first identified adenosine-9-specific tRNA methyltransferase in eukaryotes and methylates a single tRNA. Furthermore, we show that the lack of G9 methylation causes a decrease in the steady-state levels of the initiator tRNAiMet-CAT, and an alteration in its further post-transcriptional modification. In conclusion, our work sheds light on the function in vivo of the members of the TRM10 family, and provides evidence that the loss of TRMT10A can affect the cellular translation machinery.
The TRM10 family of methyltransferases is responsible for the methylation of position 9 in tRNAs in Archaea and Eukarya. The human genome encodes three enzymes of the family, of which only the mitochondrial form TRMT10C was previously characterized, whereas the function and the targets of TRMT10A and TRMT10B were not investigated so far. Here we show that TRMT10A and TRMT10B methylate a subset of nuclear-encoded tRNAs in human cells; the two enzymes have a completely distinct repertoire of targets, and show no functional redundancy. Remarkably, TRMT10A is guanosine-9 specific and methylates 11 distinct tRNAs, whilst TRMT10B is the first identified adenosine-9-specific tRNA methyltransferase in eukaryotes and methylates a single tRNA. Furthermore, we show that the lack of G9 methylation causes a decrease in the steady-state levels of the initiator tRNAiMet-CAT, and an alteration in its further post-transcriptional modification. In conclusion, our work sheds light on the function in vivo of the members of the TRM10 family, and provides evidence that the loss of TRMT10A can affect the cellular translation machinery.