# tRNA in codon usage

> **NIH NIH R35** · THOMAS JEFFERSON UNIVERSITY · 2020 · $291,505

## Abstract

PROJECT SUMMARY:
Codon usage is a specific feature of each gene and each genome and impacts the fitness of each organism. In
the degeneracy of the genetic code, proteins can be coded in multiple ways using different sets of synonymous
codons, which are not translated equally in speed or quality. Each codon choice between the synonyms makes
a demand for the supply of the tRNA with the matching anticodon. The quality of a codon-anticodon pairing
interaction is determined not only by the level of the tRNA for the codon, but also by the epigenetic
modifications to the tRNA that are synthesized post-transcriptionally. While most studies have focused on the
abundance of tRNA as a determinant of codon usage and cell fitness, less is known about post-transcriptional
modifications. In the past 5 years, my lab has focused on the N1-methylation of the guanine at position 37 that
synthesizes m1G37 in tRNAs, which is required for reading-frame maintenance during protein synthesis. Loss
of m1G37-tRNAs leads to accumulation of ribosomal +1-shifts, resulting in pre-mature termination of protein
synthesis and ultimately cell death. A key finding of our work is that, while m1G37 is required for translation of
all four codons for proline (Pro), it is essential for translation of CC[C/U] codons. Because Pro is a unique
amino acid in protein synthesis, this finding offers interesting and important new biology, in which m1G37-
tRNAs provide a global mechanism to control the expression of CC[C/U]-enriched genes. In the next frontier of
research, we will focus on the m1G37-dependent differential translation of CC[CU] as a model to elucidate the
principles by which the supply-to-demand ratio of tRNAs governs cell fitness. We will start by analysis of the
balanced growth of E. coli as a reporter for genome-wide protein synthesis. We will test the predictive power of
the elucidated principles in determining the human proteome. We will also address the role of m1G
methylation, when placed at position 9 of a pathogenic mitochondrial tRNA (mt-tRNA), in the development of
the mitochondrial disorder. By exploring the unique methodologies and conceptual frameworks that we have
developed, we will address these key gaps in the field and advance our understanding of codon usage in
human health and disease.

## Key facts

- **NIH application ID:** 9851614
- **Project number:** 1R35GM134931-01
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Ya-Ming Hou
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $291,505
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851614

## Citation

> US National Institutes of Health, RePORTER application 9851614, tRNA in codon usage (1R35GM134931-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851614. Licensed CC0.

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