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The mitochondrial methylation potential gates mitoribosome assembly
Open accessPreprint — published as 10.1038/s41467-025-60977-x · Paper page
Abstract
S-adenosylmethionine (SAM) is crucial for cellular processes, primarily serving as the principal methyl group donor of the cell and playing a key role in gene regulation and translation on the ribosome. Inside mitochondria, SAM-dependent methylations occur at several steps of gene expression, but their role and significance remain unclear. Using direct long-read RNA sequencing on mouse tissue and mouse embryonic fibroblasts, we demonstrate that the mitochondrial ribosomal gene cluster is not efficiently processed without mitochondrial SAM. This results in the accumulation of unprocessed ribosomal RNA precursors. Protein profiling of ribosome fractions revealed that these precursors are associated with processing and ribosome assembly factors, indicating stalling at an early stage. Structural analysis of the mitochondrial ribosome by cryogenic electron microscopy revealed that mitochondrial SAM is required during peptidyl transferase centre formation and mitochondrial ribosome assembly. Our data thus identify a critical role for methylation at two steps during mitochondrial gene expression.
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Sorted by citations
Singh, V., Shiriaev, D., Bilalli, L., Khawaja, A., & Rorbach, J. (2026) · Nature Communications · doi:10.1038/s41467-026-74700-x · Cited by 1
“Furthermore, it has recently been shown that mtLSU rRNA can reach a near-mature state in the absence of mitochondrial methylation potential, highlighting a non-enzymatic role of methyl transferases 35 .”
Self-citationMittoSAM-dependent lipoylation controls postnatal heart development via metabolic remodelingPreprint
Rumyantseva, A., Wilhalm, A., Carter, W., Tippetts, T. S., Moedas, M., Rosenberger, F., Moore, D., Végvári, Á., Hinze, Y., Muellner-Wong, L. S., et al. (2026) · bioRxiv · doi:10.64898/2026.04.20.719537 · Cited by 1
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Zhang, S., Han, B., Chen, L., Chen, L., Wang, T., Lin, M., Liu, J., & Wang, Y. (2026) · Clinical Cancer Bulletin · doi:10.1007/s44272-026-00071-5
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Metadata
- Authors
- Glasgow, R. I. C., Singh, V., Peña-Pérez, L., Wilhalm, A., Moedas, M. F., Moore, D., Rosenberger, F. A., Li, X., Atanassov, I., Saba, M., Cipullo, M., Rorbach, J., Wedell, A., Freyer, C., Amunts, A., & Wredenberg, A.
- Affiliations
- Karolinska Institutet (SE)
- Stockholm University (SE)
- Karolinska University Hospital (SE)
- Max Planck Institute for Biology of Ageing (DE)
- University of Münster (DE)
- Corresponding author
- Freyer, Christoph
- Amunts, Alexey
- Wredenberg, Anna
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2024-11-16
- Volume
- 16
- Issue
- 1
- Pages
- 5388-5388
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12198368
- OpenAlex
- W4411622405
- Cited by
- 14
- References
- 0
- Citations by year
- 2026: 9 · 2025: 5
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Cancerfonden (RS2022-0708, 21 1621 Pj, VR2022-01287, 2-190/2022, KAW2019.0109, NN0082202)
- Karolinska Institutet (2-190/2022)
- Knut och Alice Wallenbergs Stiftelse (KAW 2019.0109, KAW2019)
- Vetenskapsrådet (2-190/2022, RS2022-0708, 07091, 2023-07091, NN0082202, 2022-01287, 2018-, 21 1621 Pj, KAW2019.0109)
- Stockholms Universitet
- Science for Life Laboratory
- Novo Nordisk Foundation Center for Basic Metabolic Research (NN0082202)
- Uppsala Multidisciplinary Center for Advanced Computational Science
- H2020 European Research Council (805230)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- S-adenosylmethionine, mitochondrial ribosome biogenesis, SAM-dependent methylation, peptidyl transferase center, mitochondrial translation, mitochondrial gene expression, RNA methylation
- MeSH terms
- Mitochondrial Ribosomes, Animals, Fibroblasts, Methylation, Mitochondria, Ribosomal Proteins, RNA Processing, Post-Transcriptional, S-Adenosylmethionine, Cryoelectron Microscopy, Mitochondrial Proteins, Proteomics, Mice
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