MRM3 (mitochondrial rRNA methyltransferase 3) is an S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyzes 2'-O-methylguanosine formation at position 1370 (Gm1370) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA) 1. This modification occurs in the peptidyl transferase domain and is interdependent with MRM2-mediated Um1369 methylation 2. MRM3 functions as a critical assembly factor for late-stage human 39S mitoribosome biogenesis, maintaining proper 16S rRNA conformation during this process 3. Depletion of MRM3 in human cells causes respiratory incompetence through diminished mitochondrial translation and aberrant assembly of the mt-LSU 1. During human cytomegalovirus infection, MRM3 is highly upregulated as part of the viral manipulation of mitochondrial biogenesis; knockdown of MRM3 abolishes virus-mediated increases in mitochondrially encoded proteins and significantly impairs viral replication 4. A recent Mendelian randomization study identified MRM3 as a potential risk factor for sepsis and sepsis-related mortality 5. Thus, MRM3 represents an essential regulator of mitochondrial protein synthesis with implications in metabolic homeostasis, viral pathogenesis, and sepsis pathophysiology.