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 (m5C) in other RNA biotypes is still under debate. Location in RNA and function of m5C has not been studied yet. This study is aimed at identifying new m5C 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.

Location and Function of Cytosine-5 Methylation in RNA

Identification of direct targets and modified bases of RNA cytosine methyltransferases

Mutations in NSUN2 cause autosomal-recessive intellectual disability.

Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome

Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability.

Mapping and significance of the mRNA methylome