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Genome Res_Ribas_2026.pdf (7.03 MB)

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2026-04-15

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cc-by-nc (c) Cold Spring Harbor Laboratory Press., 2026
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/229915

Age-dependent mutational loads in human tRNA genes are tumor-specific and result in chimeric tRNA sequences that could disrupt the genetic code

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https://doi.org/10.1101/gr.281022.125

Resum

Transfer RNA genes (tDNAs) are essential genomic elements that safeguard translational fidelity. Using the Telomere-to-Telomere version of the human genome we have mapped the position of human tDNAs and analyzed their individual transcriptional activities. Then we have characterized, at single base resolution, the impact of somatic mutations in human tDNAs and its relationship to the transcriptional status of each gene. We confirm that tDNAs are hotspots for somatic mutagenesis, and show that they display mutational loads that are directly proportional to their transcription rates. Highly transcribed tDNAs in tumors or healthy tissues accumulate mutations at rates up to nine-fold higher than highly transcribed protein-coding genes. Mutational loads at tDNAs are tumor-specific, and increase with patient age. Mutations at structurally conserved tRNA positions appear to be under negative selection. Anticodon nucleotides crucial for decoding frequently acquire somatic mutations, readily generating chimeric tRNA species potentially capable of systematically introducing amino acid substitutions across the proteome. Our results reveal a previously unrecognized source of somatic heterogeneity in human cancer and aging tissues that may directly impact upon translation efficiency and fidelity, and cause cell-specific proteostasis degeneration

Matèries

Genoma humà, Codi genètic, Càncer

Matèries (anglès)

Human genome, Genetic code, Cancer

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Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

MURILLO RECIO, Marina, et al. Age-dependent mutational loads in human tRNA genes are tumor-specific and result in chimeric tRNA sequences that could disrupt the genetic code. Genome Research. 2026. Vol. 36, num. 6. ISSN 1088-9051. [consulted: 29 of June of 2026]. Available at: https://hdl.handle.net/2445/229915

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