Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes
Abstract While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56348-1 |
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| author | Yuko Nakano Howard Gamper Henri McGuigan Sunita Maharjan Jiatong Li Zhiyi Sun Erbay Yigit Sebastian Grünberg Keerthana Krishnan Nan-Sheng Li Joseph A. Piccirilli Ralph Kleiner Nicole Nichols Brian D. Gregory Ya-Ming Hou |
| author_facet | Yuko Nakano Howard Gamper Henri McGuigan Sunita Maharjan Jiatong Li Zhiyi Sun Erbay Yigit Sebastian Grünberg Keerthana Krishnan Nan-Sheng Li Joseph A. Piccirilli Ralph Kleiner Nicole Nichols Brian D. Gregory Ya-Ming Hou |
| author_sort | Yuko Nakano |
| collection | DOAJ |
| description | Abstract While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro—a new group-II intron-encoded RT—to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and three mouse tissues and show that, while the landscape of modifications is highly variable throughout the tRNA sequence framework, it is stabilized for modifications that are required for reading of the genetic code. The coordinated changes have fundamental importance for development of tRNA modifications in protein homeostasis. |
| format | Article |
| id | doaj-art-36ac901a69e84057b506760810ffab33 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-36ac901a69e84057b506760810ffab332025-01-26T12:40:25ZengNature PortfolioNature Communications2041-17232025-01-0116111910.1038/s41467-025-56348-1Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changesYuko Nakano0Howard Gamper1Henri McGuigan2Sunita Maharjan3Jiatong Li4Zhiyi Sun5Erbay Yigit6Sebastian Grünberg7Keerthana Krishnan8Nan-Sheng Li9Joseph A. Piccirilli10Ralph Kleiner11Nicole Nichols12Brian D. Gregory13Ya-Ming Hou14Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityDepartment of Biochemistry and Molecular Biology, Thomas Jefferson UniversityDepartment of Biochemistry and Molecular Biology, Thomas Jefferson UniversityDepartment of Biochemistry and Molecular Biology, Thomas Jefferson UniversityDepartment of Biology, University of PennsylvaniaNew England BiolabsNew England BiolabsNew England BiolabsNew England BiolabsDepartment of Biochemistry & Molecular Biology, University of ChicagoDepartment of Biochemistry & Molecular Biology, University of ChicagoDepartment of Chemistry, Princeton UniversityNew England BiolabsDepartment of Biology, University of PennsylvaniaDepartment of Biochemistry and Molecular Biology, Thomas Jefferson UniversityAbstract While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro—a new group-II intron-encoded RT—to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and three mouse tissues and show that, while the landscape of modifications is highly variable throughout the tRNA sequence framework, it is stabilized for modifications that are required for reading of the genetic code. The coordinated changes have fundamental importance for development of tRNA modifications in protein homeostasis.https://doi.org/10.1038/s41467-025-56348-1 |
| spellingShingle | Yuko Nakano Howard Gamper Henri McGuigan Sunita Maharjan Jiatong Li Zhiyi Sun Erbay Yigit Sebastian Grünberg Keerthana Krishnan Nan-Sheng Li Joseph A. Piccirilli Ralph Kleiner Nicole Nichols Brian D. Gregory Ya-Ming Hou Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes Nature Communications |
| title | Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes |
| title_full | Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes |
| title_fullStr | Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes |
| title_full_unstemmed | Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes |
| title_short | Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes |
| title_sort | genome wide profiling of trna modifications by induro trnaseq reveals coordinated changes |
| url | https://doi.org/10.1038/s41467-025-56348-1 |
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