NSUN5

NSUN5, or NOP2/Sun domain family member 5, is a protein-coding gene in humans that encodes an RNA cytosine-5 methyltransferase. It belongs to the NSUN family of enzymes that catalyze the formation of 5-methylcytosine (m5C) in RNA substrates, including ribosomal RNA and transfer RNA, using S-adenosyl-L-methionine as the methyl donor. The protein contains the conserved catalytic motifs of cytosine-5 methyltransferases and a Sun domain, and is thought to operate in the nucleolus as part of ribosome biogenesis.

Functionally, NSUN5 is implicated in the methylation of cytosines in ribosomal RNA, a modification that can affect rRNA structure, stability, and ribosome assembly. In model systems, loss or reduction of NSUN5 activity lowers m5C levels in rRNA and can perturb ribosome maturation and function, linking its activity to protein synthesis capacity.

In humans, NSUN5 is widely expressed with higher apparent activity in tissues with active ribosome production. The protein localizes predominantly to the nucleolus, consistent with a role in ribosome biogenesis, and may interact with other ribosome-associated factors during rRNA processing.

Clinical significance is an area of active study. Rare variants or dysregulation of NSUN5 have been reported in individuals with neurodevelopmental disorders and intellectual disability in some lines of research, though the full contribution of NSUN5 to disease remains under investigation. As with many RNA-modifying enzymes, the biological impact of altered NSUN5 activity likely involves changes to ribosome function and protein synthesis.

See also: NSUN family; RNA methylation; ribosome biogenesis.