Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines
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 p...
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022005773 |
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| author | Florian Pichot Marion C. Hogg Virginie Marchand Valérie Bourguignon Elisabeth Jirström Cliona Farrell Hesham A. Gibriel Jochen H.M. Prehn Yuri Motorin Mark Helm |
| author_facet | Florian Pichot Marion C. Hogg Virginie Marchand Valérie Bourguignon Elisabeth Jirström Cliona Farrell Hesham A. Gibriel Jochen H.M. Prehn Yuri Motorin Mark Helm |
| author_sort | Florian Pichot |
| collection | DOAJ |
| description | 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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| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:31:02Z |
| publishDate | 2023-01-01 |
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| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-5444ab864f174edf9600ecf2715a0d802023-12-21T07:30:29ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-0121401417Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-linesFlorian Pichot0Marion C. Hogg1Virginie Marchand2Valérie Bourguignon3Elisabeth Jirström4Cliona Farrell5Hesham A. Gibriel6Jochen H.M. Prehn7Yuri Motorin8Mark Helm9Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128 Mainz, Germany; Université de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, FranceDepartment of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, IrelandUniversité de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, FranceUniversité de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, France; Université de Lorraine, CNRS, IMoPA (UMR7365), F54000 Nancy, FranceDepartment of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, IrelandDepartment of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, IrelandDepartment of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, IrelandDepartment of Physiology and Medical Physics and SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, D02 YN77, IrelandUniversité de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, France; Université de Lorraine, CNRS, IMoPA (UMR7365), F54000 Nancy, France; Corresponding author at: Université de Lorraine, CNRS, INSERM, IBSLor (UAR2008/US40), Epitranscriptomics and RNA Sequencing Core Facility, F54000 Nancy, France.Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128 Mainz, Germany; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2001037022005773TRNAModificationTRNA fragmentsAngiogeninModification mappingRNAseq |
| spellingShingle | Florian Pichot Marion C. Hogg Virginie Marchand Valérie Bourguignon Elisabeth Jirström Cliona Farrell Hesham A. Gibriel Jochen H.M. Prehn Yuri Motorin Mark Helm Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines Computational and Structural Biotechnology Journal TRNA Modification TRNA fragments Angiogenin Modification mapping RNAseq |
| title | Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines |
| title_full | Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines |
| title_fullStr | Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines |
| title_full_unstemmed | Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines |
| title_short | Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines |
| title_sort | quantification of substoichiometric modification reveals global tsrna hypomodification preferences for angiogenin mediated trna cleavage and idiosyncratic epitranscriptomes of human neuronal cell lines |
| topic | TRNA Modification TRNA fragments Angiogenin Modification mapping RNAseq |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022005773 |
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