# Determining the influence of codon optimality on mRNA translation and decay

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $323,406

## Abstract

Abstract
Messenger RNA degradation represents a critical step in the regulation of gene expression.
While the major pathways and enzymes catalyzing mRNA turnover have been identified,
accounting for disparate half-lives has been elusive. Recently, we have discovered that codon
optimality is a major feature that contributes greatly to mRNA stability. Codon optimality is a
term to describe the fact that tRNA levels are not the same in the cell. Thus is it predicted that
each of the 61 codons is read by the ribosome at a slightly different rate. Codons whose
tRNA levels are high are termed optimal codons, while codons whose tRNA levels are low are
termed non-optimal codons. Genome-wide RNA decay analysis revealed that stable mRNAs
are enriched in codons designated optimal, whereas unstable mRNAs contain predominantly
non-optimal codons. Substitution of optimal codons with synonymous, non-optimal codons
results in dramatic mRNA destabilization, while the converse substitution significantly increases
stability. Further, we show that optimal codon content accounts for the similar stabilities
observed in mRNAs encoding proteins with coordinated physiological function. We suggest that
codon optimality impacts ribosome translocation, connecting the processes of translation
elongation and decay. This work demonstrates that the degeneracy in the genetic code exists as
a mechanism to finely tune levels of mRNAs, and ultimately, proteins through codon optimality.
We will continue to investigate the influence of codon optimality on gene expression in this
proposal.

## Key facts

- **NIH application ID:** 10177318
- **Project number:** 7R01GM118018-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jeffery Coller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $323,406
- **Award type:** 7
- **Project period:** 2017-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177318

## Citation

> US National Institutes of Health, RePORTER application 10177318, Determining the influence of codon optimality on mRNA translation and decay (7R01GM118018-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10177318. Licensed CC0.

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