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Glasgow RIC, Singh V, Peña-Pérez L, Wilhalm A, Moedas MF, Moore D, Rosenberger FA, Li X, Atanassov I, Saba M, Cipullo M, Rorbach J, Wedell A, Freyer C, Amunts A, Wredenberg A
Nat Commun 16 (1) 5388 [2025-06-25; online 2025-06-25]
S-adenosylmethionine (SAM) is the principal methyl donor in cells and is essential for mitochondrial gene expression, influencing RNA modifications, translation, and ribosome biogenesis. Using direct long-read RNA sequencing in mouse tissues and embryonic fibroblasts, we show that processing of the mitochondrial ribosomal gene cluster fails in the absence of mitochondrial SAM, leading to an accumulation of unprocessed precursors. Proteomic analysis of ribosome fractions revealed these precursors associated with processing and assembly factors, indicating stalled biogenesis. Structural analysis by cryo-electron microscopy demonstrated that SAM-dependent methylation is required for peptidyl transferase centre formation during mitoribosome assembly. Our findings identify a critical role for SAM in coordinating mitoribosomal RNA processing and large subunit maturation, linking cellular methylation potential to mitochondrial translation capacity.
NGI Uppsala (Uppsala Genome Center) [Service]
National Genomics Infrastructure [Service]
PubMed 40562754
DOI 10.1038/s41467-025-60977-x
Crossref 10.1038/s41467-025-60977-x
pmc: PMC12198368
pii: 10.1038/s41467-025-60977-x