Genome-Wide Profiling of tRNA Modifications by Induro-tRNAseq Reveals Coordinated Changes

Authors

Yuko Nakano, Thomas Jefferson UniversityFollow
Howard Gamper, Thomas Jefferson UniversityFollow
Henri McGuigan, Thomas Jefferson UniversityFollow
Sunita Maharjan, Thomas Jefferson UniversityFollow
Jiatong Li
Zhiyi Sun
Erbay Yigit
Sebastian Grünberg
Keerthana Krishnan
Nan-Sheng Li
Joseph Piccirilli
Ralph Kleiner
Nicole Nichols
Brian Gregory
Ya-Ming Hou, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

1-26-2025

Comments

This article is the author's final published version in Nature communications, Volume 16, Issue 1, 2025, Article number 1047.

The published version is available at https://doi.org/10.1038/s41467-025-56348-1.

Copyright © The Author(s) 2025

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.

Recommended Citation

Nakano, Yuko; Gamper, Howard; McGuigan, Henri; Maharjan, Sunita; Li, Jiatong; Sun, Zhiyi; Yigit, Erbay; Grünberg, Sebastian; Krishnan, Keerthana; Li, Nan-Sheng; Piccirilli, Joseph; Kleiner, Ralph; Nichols, Nicole; Gregory, Brian; and Hou, Ya-Ming, "Genome-Wide Profiling of tRNA Modifications by Induro-tRNAseq Reveals Coordinated Changes" (2025). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 276.
https://jdc.jefferson.edu/bmpfp/276

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

39865096

Language

English