Abstract Specific deposition of RNA modifications is important for regulating gene expression1,2. 5-Methylcytosine (m5C) is a common epitranscriptomic modification, and NSUN2 is a key enzyme responsible for m5C methylation of various types of RNA. Dysregulation of NSUN2 is associated with numerous diseases, including cancers and neurological disorders3. The versatility of NSUN2 complicates our understanding of its substrate specificity and molecular roles in biology and disease.
