Dataset Information

M³C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.

ABSTRACT: The epitranscriptome includes a diversity of RNA modifications that influence gene expression. N3-methylcytidine (m³C) mainly occurs in the anticodon loop (position C32) of certain tRNAs yet its role is poorly understood. Here, using HAC-Seq, we report comprehensive METTL2A/2B-, METTL6-, and METTL2A/2B/6-dependent m³C profiles in human cells. METTL2A/2B modifies tRNA-arginine and tRNA-threonine members, whereas METTL6 modifies the tRNA-serine family. However, decreased m³C32 on tRNA-Ser-GCT isodecoders is only observed with combined METTL2A/2B/6 deletion. Ribo-Seq reveals altered translation of genes related to cell cycle and DNA repair pathways in METTL2A/2B/6-deficient cells, and these mRNAs are enriched in AGU codons that require tRNA-Ser-GCT for translation. These results, supported by reporter assays, help explain the observed altered cell cycle, slowed proliferation, and increased cisplatin sensitivity phenotypes of METTL2A/2B/6-deficient cells. Thus, we define METTL2A/2B/6-dependent methylomes and uncover a particular requirement of m³C32 tRNA modification for serine codon-biased mRNA translation of cell cycle, and DNA repair genes.

SUBMITTER: Cui J

PROVIDER: S-EPMC11233606 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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m3C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.

Cui Jia J Sendinc Erdem E Liu Qi Q Kim Sujin S Fang Jaden Y JY Gregory Richard I RI

Nature communications 20240710 1

The epitranscriptome includes a diversity of RNA modifications that influence gene expression. N3-methylcytidine (m3C) mainly occurs in the anticodon loop (position C32) of certain tRNAs yet its role is poorly understood. Here, using HAC-Seq, we report comprehensive METTL2A/2B-, METTL6-, and METTL2A/2B/6-dependent m3C profiles in human cells. METTL2A/2B modifies tRNA-arginine and tRNA-threonine members, whereas METTL6 modifies the tRNA-serine family. However, decreased m<su ...[more]

PMID: 38982125

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Project description:tRNA (tRNA) is a key molecule used for protein synthesis, with multiple points of stress-induced regulation that can include transcription, transcript processing, localization and ribonucleoside base modification. Enzyme-catalyzed modification of tRNA occurs at a number of base and sugar positions and has the potential to influence specific anticodon-codon interactions and regulate translation. Notably, altered tRNA modification has been linked to mitochondrial diseases and cancer progression. In this review, specific to Eukaryotic systems, we discuss how recent systems-level analyses using a bioanalytical platform have revealed that there is extensive reprogramming of tRNA modifications in response to cellular stress and during cell cycle progression. Combined with genome-wide codon bias analytics and gene expression studies, a model emerges in which stress-induced reprogramming of tRNA drives the translational regulation of critical response proteins whose transcripts display a distinct codon bias. Termed Modification Tunable Transcripts (MoTTs), (1) we define them as (1) transcripts that use specific degenerate codons and codon biases to encode critical stress response proteins, and (2) transcripts whose translation is influenced by changes in wobble base tRNA modification. In this review we note that the MoTTs translational model is also applicable to the process of stop-codon recoding for selenocysteine incorporation, as stop-codon recoding involves a selective codon bias and modified tRNA to decode selenocysteine during the translation of a key subset of oxidative stress response proteins. Further, we discuss how in addition to RNA modification analytics, the comprehensive characterization of translational regulation of specific transcripts requires a variety of tools, including high coverage codon-reporters, ribosome profiling and linked genomic and proteomic approaches. Together these tools will yield important new insights into the role of translational elongation in cell stress response.

Dataset Information

M³C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.

Publications

m<sup>3</sup>C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.

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M3C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.

Publications

m<sup>3</sup>C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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M³C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.