# Molecular Basis of Ribosomal Frameshifting

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $25,120

## Abstract

Ribosomes are the complex, cellular machinery responsible for promoting mRNA-directed translation of the
genetic code to produce all proteins in every living organism. The ribosome must select correct tRNAs to
decode the mRNA, facilitate peptide bond formation, and then move the tRNAs through its three functionally
distinct tRNA binding sites in a dynamic and exquisitely orchestrated manner. Errors associated with this
process of protein synthesis are detrimental to gene expression and hence cellular function. Therefore,
accurate maintenance of the universal mRNA three-nucleotide code (or “reading frame”) by the ribosome is
critical but the molecular details of how this is controlled, or deviated from in a programmed manner, is not well
understood. The mechanism of mRNA frame maintenance and how RNAs including tRNAs and mRNA
collaborate to prevent mRNA shifting remains unknown. Our preliminary data reveals that frameshift
suppressor tRNAs cause +1 frameshifting their biased position towards the E site post decoding that pulls the
30S head domain incompatible with elongation factor binding. In Aim 1, we will determine how endogenous
tRNA modifications located at position 37 regulate the mRNA frame. Next, we will determine how elongation
factors recognize a ribosome complex undergoing frameshifting and whether these factors play regulatory
roles in mRNA frame maintenance. In Aim 3 we will identify how initiator tRNAfMet and initiation factors
collaborate to maintain the mRNA AUG start frame. In Aim 4, we will study two different mRNAs that control
gene expression. Together these aims will be accomplished through a combination of structural biology of
large, functional ribosomal complexes and biochemical methods such as smFRET and RNA SHAPE probing.

## Key facts

- **NIH application ID:** 10388809
- **Project number:** 3R01GM093278-12S2
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Christine M Dunham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $25,120
- **Award type:** 3
- **Project period:** 2010-06-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388809

## Citation

> US National Institutes of Health, RePORTER application 10388809, Molecular Basis of Ribosomal Frameshifting (3R01GM093278-12S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10388809. Licensed CC0.

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