The yeast RNA methylation complex consists of conserved yet reconfigured components with m6A-dependent and independent roles
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Abstract
N6 -methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/insects/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis and was known to comprise three proteins, of which two were conserved. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2). All MTC subunits, except for Dyn2, are essential for m6A deposition and have corresponding mammalian MTC orthologues. Unlike the mammalian bipartite MTC, the yeast MTC is unipartite, yet multifunctional. The mRNA interacting module, comprising Ime4, Mum2, Vir1, and Kar4, exerts the MTC’s m6A-independent function, while Slz1 enables the MTC catalytic function in m6A deposition. Both functions are critical for meiotic progression. Kar4 also has a mechanistically separate role from the MTC during mating. The yeast MTC constituents play distinguishable m6A-dependent, MTC-dependent, and MTC-independent functions, highlighting their complexity and paving the path towards dissecting multi-layered MTC functions in mammals.
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Cites
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- Authors
- Ensinck, I., Maman, A., Albihlal, W. S., Lassandro, M., Salzano, G., Sideri, T., Howell, S. A., Calvani, E., Patel, H., Bushkin, G., Ralser, M., Snijders, A. P., Skehel, M., Casañal, A., Schwartz, S., & van Werven, F. J.
- Affiliations
- The Francis Crick Institute (GB)
- Weizmann Institute of Science (IL)
- Human Technopole (IT)
- Whitehead Institute for Biomedical Research (US)
- The Francis Crick Institute
- Corresponding author
- Schwartz, Schraga
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-07-25
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC10393049
- OpenAlex
- W4379015599
- Cited by
- 21
- References
- 6
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 5
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust (FC001203)
- Cancer Research UK (FC001203)
- Medical Research Council (FC001203)
- Israel Science Foundation (913/21)
- European Research Council (714023, 101000970)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- m6A methyltransferase complex, yeast, meiosis, mating, protein complex composition
- MeSH terms
- Meiosis, Methylation, RNA, Messenger, Yeasts, Gene Expression
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