FTSJ3 is an RNA 2'-O-methyltransferase that functions in both ribosomal RNA processing and viral immune evasion. In normal cellular function, FTSJ3 localizes to the nucleolus and participates in pre-rRNA processing, particularly affecting 18S rRNA maturation through processing of sites A0, 1, and 2 1. The enzyme associates with NIP7 during ribosome biogenesis and is required for proper cell proliferation 1. FTSJ3 also regulates R-loop homeostasis, preventing R-loop-associated DNA damage and maintaining genomic stability 2. In viral infections, particularly HIV-1, FTSJ3 is recruited to viral RNA through interaction with TARBP2/TRBP and catalyzes 2'-O-methylation of the viral genome with preference for adenosine residues 3. This methylation allows HIV-1 to evade innate immune recognition by IFIH1/MDA5 and reduces type I interferon responses 34. The methylation also protects viral RNA from ISG20 nuclease degradation 4. In cancer, FTSJ3 is upregulated and promotes immune evasion by suppressing dsRNA-induced IFNβ signaling, with FTSJ3 deletion enhancing anti-PD-1 immunotherapy efficacy 5. Paradoxically, viral RNA methylation by FTSJ3 can impair HIV-1 reverse transcription, suggesting complex regulatory effects during viral replication 6.