Linder, Bastian and Sharma, Puneet and Wu, Jie and Birbaumer, Tosca and Eggers, Cristian and Murakami, Shino and Ott, Roman E. and Fenzl, Kai and Vorgerd, Hannah and Erhard, Florian and Jaffrey, Samie R. and Leidel, Sebastian A. and Steinmetz, Lars M. (2025) tRNA modifications tune m6A-dependent mRNA decay. CELL, 188 (14). pp. 3715-3727. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)Abstract
Chemically modified nucleotides in mRNA are critical regulators of gene expression, primarily through interactions with reader proteins that bind to these modifications. Here, we present a mechanism by which the epitranscriptomic mark N6-methyladenosine (m6A) is read by tRNAs during translation. Codons that are modified with m6A are decoded inefficiently by the ribosome, rendering them "non-optimal"and inducing ribosome collisions on cellular transcripts. This couples mRNA translation to decay. 5-Methoxycarbonylmethyl-2-thiouridine (mcm5s2U) in the tRNA anticodon loop counteracts this effect. This unanticipated link between the mRNA and tRNA epitranscriptomes enables the coordinated decay of mRNA regulons, including those encoding oncogenic signaling pathways. In cancer, dysregulation of the m6A and mcm5s2U biogenesis pathways-marked by a shift toward more mcm5s2U-is associated with more aggressive tumors and poor prognosis. Overall, this pan-epitranscriptomic interaction represents a novel mechanism of post-transcriptional gene regulation with implications for human health.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSLATION-ELONGATION; WOBBLE POSITION; IN-VIVO; M(6)A; REVEALS; METHYLATION; N-6-METHYLADENOSINE; COORDINATION; RECOGNITION; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Informatics and Data Science > Department Computational Life Science > Chair of Computational Immunology (Prof. Dr. Florian Erhard) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2026 09:46 |
| Last Modified: | 01 Apr 2026 09:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67740 |
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