Location and Function of NSun2-Mediated Cytosine-5 Methylation in RNA

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.

• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• Total number of consented subjects: 2
• Subject Sample Telemetry Report (SSTR)

Please refer to study "Ciliopathies Exome Sequencing Initiative" (dbGaP Study Accession: phs000288.v1.p1)

March 2012 - Release of Ciliopathies Exome Sequencing Initiative (dbGaP Study Accession: phs000288.v1.p1)

June 2012 - Publication of the study Martinez FJ, Lee JH, et al. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet. 2012 Jun;49(6):380-5 (PMID: 22577224).

• Primary Phenotype: Dubowitz Syndrome

• Principal Investigator
  • Michaela Frye, PhD. WT-MRC-Stem Cell Institute, Cambridge, UK.
• Funding Source
  • Cancer Research UK: "Cytosine-5 RNA methylation in normal and cancer stem cells". WT-MRC-Stem Cell Institute, Cambridge, UK.
  • European Research Council: "m5C RNA". WT-MRC-Stem Cell Institute, Cambridge, UK.