# Regulation and function of bacterial 100S ribosome

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $329,258

## Abstract

SUMMARY
 During bacterial protein synthesis, the 30S and 50S ribosomal subunits assemble into the translationally
active 70S ribosome on template mRNA. In the Gram-positive human bacterial pathogen Staphylococcus
aureus, a single small ribosome-binding protein called hibernation-promoting factor (HPFSa) stimulates the
dimerization of 2.5-MDa 70S monomers to form the translationally silent 100S complex. The physiological
function of the 100S ribosome remains enigmatic because the temporal abundance of the 100S ribosome
varies considerably among different bacterial phyla, the global impact of the 100S ribosome on translation is
completely unknown, and hpf null mutants of different bacteria lack a common phenotype. Moreover, distantly
related gammaproteobacteria, such as E. coli, require two proteins (RMFEc and HPFEc) to achieve 100S
complex formation. Recent data from our group demonstrate that HPFSa is essential for the bacterial survival
and maintenance of the ribosome pool in aging S. aureus cells. Surprisingly, eliminating hpfSa causes the
derepression of only a subset of genes at translational initiation. Our goal is to establish a mechanistic
understanding of the function of the 100S ribosome in translational capacity and staphylococcal pathogenesis.
We will take a multi-disciplinary approach that spans genetics, molecular biophysics, biochemistry, and whole
animal infection studies. Aim 1 will determine the process and factors involved in the reversible conversion of
70S and 100S ribosomes. Aim 2 will determine how the HPFSa/100S ribosome inhibits translation in a gene-
specific manner. Aim 3 will identify the roles of the 100S complex in ribosome turnover and staphylococcal
pathophysiology. These aims have the potential to produce novel insights into ribosome metabolism and
inspire alternate treatments for persistent and relapsed staphylococcal infections that are intimately linked to
survive for an extended period inside the host.

## Key facts

- **NIH application ID:** 9987654
- **Project number:** 5R01GM121359-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** M.-N. Frances Yap
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $329,258
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987654

## Citation

> US National Institutes of Health, RePORTER application 9987654, Regulation and function of bacterial 100S ribosome (5R01GM121359-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987654. Licensed CC0.

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