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Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines.
Pichot, Florian; Hogg, Marion C; Marchand, Virginie; Bourguignon, Valérie; Jirström, Elisabeth; Farrell, Cliona; Gibriel, Hesham A; Prehn, Jochen H M; Motorin, Yuri; Helm, Mark.
Affiliation
  • Pichot F; Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128 Mainz, Germany.
  • Hogg MC; Université de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, France.
  • Marchand V; Department of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, Ireland.
  • Bourguignon V; Université de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, France.
  • Jirström E; Université de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, France.
  • Farrell C; Université de Lorraine, CNRS, IMoPA (UMR7365), F54000 Nancy, France.
  • Gibriel HA; Department of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, Ireland.
  • Prehn JHM; Department of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, Ireland.
  • Motorin Y; Department of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, Ireland.
  • Helm M; Department of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, Ireland.
Comput Struct Biotechnol J ; 21: 401-417, 2023.
Article in En | MEDLINE | ID: mdl-36618980
Modification of tRNA is an integral part of the epitranscriptome with a particularly pronounced potential to generate diversity in RNA expression. Eukaryotic tRNA contains modifications in up to 20% of their nucleotides, but not all sites are always fully modified. Combinations and permutations of partially modified sites in tRNAs can generate a plethora of tRNA isoforms, termed modivariants. Here, we investigate the stoichiometry of incompletely modified sites in tRNAs from human cell lines for their information content. Using a panel of RNA modification mapping methods, we assess the stoichiometry of sites that contain the modifications 5-methylcytidine (m5C), 2'-O-ribose methylation (Nm), 3-methylcytidine (m3C), 7-methylguanosine (m7G), and Dihydrouridine (D). We discovered that up to 75% of sites can be incompletely modified and that the differential modification status of a cellular tRNA population holds information that allows to discriminate e.g. different cell lines. As a further aspect, we investigated potential causal connectivity between tRNA modification and its processing into tRNA fragments (tiRNAs and tRFs). Upon exposure of cultured living cells to cell-penetrating angiogenin, the modification patterns of the corresponding RNA populations was changed. Importantly, we also found that tsRNAs were significantly less modified than their parent tRNAs at numerous sites, suggesting that tsRNAs might derive chiefly from hypomodified tRNAs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Comput Struct Biotechnol J Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Comput Struct Biotechnol J Year: 2023 Document type: Article Affiliation country: Country of publication: