phs000645
Loss of cytosine-5 methylation in tRNA triggers stress responses in a disease model for Intellectual Disabilities
Mutations in the cytosine-5 RNA methyltransferase NSun2 can cause neurodevelopmental disorders and symptoms commonly found in patients with Dubowitz-like syndrome. Some tRNAs are known to be methylated NSun2, however the occurrence of cytosine-5 methylation (m<sup>5</sup>C) in other RNA biotypes is still under debate. Location in RNA and function of m<sup>5</sup>C has not been studied yet. This study is aimed at identifying new m<sup>5</sup>C methylated RNA biotypes, as well as the location at specific structures or sequences and the ultimate biological function. The impact of the loss of NSun2-mediated methylation is also determined by comparing gene expression data with the global cytosine-5 RNA methylome in Dubowitz-like syndrome patients. We also use ribosomal profiling to assess the impact of the loss and rescue of Nsun2-mediated cytosine-5 RNA methylation on translation rates and ribosome occupancy.