# Structural Dynamics of Translation

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $348,029

## Abstract

Abstract
 Ribosomal movement along mRNA is an essential facet of protein synthesis in all organisms. During
translation elongation the ribosome moves along mRNA in a codon-by-codon manner and unwinds mRNA
secondary structure. However, specific mRNA sequences induce ribosome stalling and frameshifting. We aim
to understand why these specific RNA sequences slow down ribosome translocation while the ribosome
translocates through most mRNA structure without long pauses. Using single-molecule fluorescence
microscopy and an in vitro translation system assembled from purified components, we will define properties of
frameshift-inducing RNA stem-loops and Shine-Dalgarno-like sequences that are critical for the ribosome
pausing. Elucidating the role of RNA structure in the modulation of translation elongation is a key to
understanding the molecular mechanism of ribosome frameshifting, which is essential for the synthesis of
numerous bacterial, eukaryotic and viral proteins. For example, the production of protease, reverse
transcriptase and integrase of human immunodeficiency virus (HIV) depends on a -1 programmed ribosomal
frameshifting event. Furthermore, ribosome pausing is a major determinant of numerous co-translational
processes including protein processing, folding and targeting to membranes. Modulation of the translation
elongation rate also affects mRNA stability and regulates levels of the produced protein.
 In addition to codon-by-codon translocation, another type of ribosome movement termed ribosome scanning
occurs during the initiation phase of protein synthesis in eukaryotes. It is believed that during eukaryotic
translation initiation the small ribosomal subunit is first recruited to the 5' end of mRNA and then scans the 5'-
untranslated region (5'UTR) of the mRNA for the start codon. The molecular mechanism of scanning, which is
critical for correct start codon selection, is poorly understood. Furthermore, the real-time movement of the
small ribosomal subunit along the 5'UTR was never detected. We will use a single-molecule fluorescence
microscopy assay designed to detect the movement of the small ribosomal subunit and measure the rate of the
scanning. We will examine the mechanism of ribosome scanning and gain critical insights into eukaryotic
translation initiation, deregulation of which is linked to a number of human diseases including cancer and
diabetes.
 Taken together, the proposed studies will substantially contribute to establishing the molecular mechanisms
of protein synthesis and provide a basis for the future development of antiviral and cancer therapies.

## Key facts

- **NIH application ID:** 9975862
- **Project number:** 5R01GM099719-09
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Dmitri Ermolenko
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,029
- **Award type:** 5
- **Project period:** 2012-04-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975862

## Citation

> US National Institutes of Health, RePORTER application 9975862, Structural Dynamics of Translation (5R01GM099719-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975862. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*