# Regulation and function of bacterial 100S ribosome

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $132,791

## Abstract

PROJECT 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:** 10241091
- **Project number:** 3R01GM121359-04S1
- **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:** $132,791
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241091

## Citation

> US National Institutes of Health, RePORTER application 10241091, Regulation and function of bacterial 100S ribosome (3R01GM121359-04S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10241091. Licensed CC0.

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