A domain of the actin binding protein Abp140 is the yeast methyltransferase responsible for 3-methylcytidine modification in the tRNA anti-codon loop
Open accessAbstract
The 3-methylcytidine (m 3 C) modification is widely found in eukaryotic species of tRNA Ser, tRNA Thr, and tRNA Arg; at residue 32 in the anti-codon loop; and at residue e2 in the variable stem of tRNA Ser. Little is known about the function of this modification or about the specificity of the corresponding methyltransferase, since the gene has not been identified. We have used a primer extension assay to screen a battery of methyltransferase candidate knockout strains in the yeast Saccharomyces cerevisiae, and find that tRNA Thr(IGU) from abp140-Δ strains lacks m 3 C. Curiously, Abp140p is composed of a poorly conserved N-terminal ORF fused by a programed +1 frameshift in budding yeasts to a C-terminal ORF containing an S-adenosylmethionine (SAM) domain that is highly conserved among eukaryotes. We show that ABP140 is required for m 3 C modification of substrate tRNAs, since primer extension is similarly affected for all tRNA species expected to have m 3 C and since quantitative analysis shows explicitly that tRNA Thr(IGU) from an abp140-Δ strain lacks m 3 C. We also show that Abp140p (now named Trm140p) purified after expression in yeast or Escherichia coli has m 3 C methyltransferase activity, which is specific for tRNA Thr(IGU) and not tRNA Phe and occurs specifically at C 32. We suggest that the C-terminal ORF of Trm140p is necessary and sufficient for activity in vivo and in vitro, based on analysis of constructs deleted for most or all of the N-terminal ORF. We also suggest that m 3 C has a role in translation, since trm140-Δ trm1-Δ strains (also lacking m 2,2 G 26) are sensitive to low concentrations of cycloheximide.
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The catalytic mutants of METTL8 failed to recruit ASCC3 to nucleoli.
“Conversely, two catalytic mutations targeting the putative SAM-binding domain of METTL8 (D’Silva et al., 2011; Noma et al., 2011) (G204A/G206A and D230A; Supplemental Figure S2a–S2c) failed to recruit ASCC3 to nucleoli”
From Aberrant RNA methylation triggers recruitment of an alkylation repair complex (2021) · cites this paper as D’Silva et al., 2011
The citation is attached to the description of a putative SAM-binding domain, not directly to the recruitment result. The Discussion describes a conserved SAM-methyltransferase domain in yeast Trm140p, but our copy does not address METTL8 catalytic mutants, ASCC3, or nucleolar recruitment (searched those terms and the specified mutations). (LLM, conf=0.78)
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Aberrant RNA methylation triggers recruitment of an alkylation repair complex
Tsao, N., Brickner, J. R., Rodell, R., Ganguly, A., Wood, M., Oyeniran, C., Ahmad, T., Sun, H., Bacolla, A., Zhang, L., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.09.024 · Cited by 46 · see citing works
- Authors
- D'Silva, S., Haider, S. J., & Phizicky, E. M.
- Affiliations
- University of Rochester Medicine (US)
- ORCID
- Phizicky, Eric M.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-04-25
- Volume
- 17
- Issue
- 6
- Pages
- 1100-1110
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC3096042
- OpenAlex
- W2097843864
- Semantic Scholar
- 7ccfaefe663148bcaab4548efe20996402a8b3bc
- Cited by
- 83
- References
- 47
- Citations by year
- 2025: 2 · 2024: 8 · 2023: 3 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 5
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Carnegie Mellon University
- Cancer Research UK
- National Institutes of Health
- National Institute of General Medical Sciences (GM52347, R01GM052347)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- tRNA modification, methyltransferase, Saccharomyces cerevisiae, translation (biology), cycloheximide sensitivity
- MeSH terms
- Anticodon, Cytidine, Microfilament Proteins, Nucleic Acid Conformation, RNA, Transfer, tRNA Methyltransferases, S-Adenosylmethionine, Saccharomyces cerevisiae, Protein Structure, Tertiary, Saccharomyces cerevisiae Proteins
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