28S rRNA cytosine-C(5) methyltransferase (NSUN5) (NSUN5)

NSUN5 is a highly conserved rRNA methyltransferase that catalyzes the methylation of cytosine 3782 in human 28S rRNA (and homologous sites in other species), regulating ribosome structure and global protein synthesis[1][2][3]. Its functional activity depends on conserved cysteine residues essential for catalysis and RNA binding/release[3][4]. NSUN5 localizes to nucleoli, where rRNA is transcribed and processed[3]. Loss or mutation of NSUN5 reduces rRNA methylation, impairs global protein translation but not ribosome biogenesis or translational fidelity, and is associated with cell growth defects[3]. It has disease relevance in cancer (e.g., glioma, colorectal cancer) where its expression promotes cell proliferation, and in Williams-Beuren syndrome where its deletion is linked to neurodevelopmental phenotypes[2][4]. NSUN5's newly emergent role also includes modulation of immune evasion pathways in glioma, adding therapeutic interest[4].

Other names

28S rRNA (cytosine-C(5))-methyltransferaseNSUN5AWBSCR20NOL1Rp120(NOL1)Williams-Beuren syndrome chromosomal region 20A proteinNOP2/Sun domain family member 5NOL1NOL1-related protein

Drugs targeting NSUN5 would theoretically act by inhibiting rRNA methylation, suppressing ribosome function, and reducing translation, with implications for cancer proliferation and immune modulation[2][4].