# Regulation and function of bacterial hibernating 100S ribosome

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $336,891

## Abstract

PROJECT SUMMARY
 Ribosome hibernation is a conserved mechanism used by both bacteria and eukaryotes to prevent translation
and to extend organismal lifespan. Recent studies from various bacterial species, including pathogenic
Staphylococcus aureus, have provided compelling evidence for a critical role of hibernating 100S ribosomes in
protecting the ribosomal pool from damage, in addition to blocking translational initiation. We found that S. aureus
ribosomes lacking hibernation-promoting factor (HPF) are rapidly degraded by the 3’-5’ exonuclease RNase
R and other hitherto unknown ribonucleases. In our unpublished work, we isolated an additional ribonuclease
mutant that rescues the loss of ribosomes in S. aureus. Surprisingly, we found that ribosomes are not the only
target of S. aureus HPF; instead, HPF could interact with a cytoplasmic protein of unknown biological activity,
thereby reducing the abundance of hibernating 100S ribosomes. We further demonstrated that HPF is restricted
to a specific subcellular localization during rapid growth, providing a rare glimpse of possible HPF segregation
from actively translating ribosomes. In this proposal, we will undertake a highly multidisciplinary approach
consisting of structural biology, omics, bacterial genetics, biochemistry and high-resolution microscopy to
achieve the following goals: (1) Determine the molecular mechanisms by which HPF protects ribosomes from
ribonucleolytic cleavage. (2) Determine the previously undiscovered extraribosomal role of HPF. (3) Determine
how the spatiotemporal localization of HPF avoids translation conflicts. HPF and RNase R are evolutionarily
conserved virulence factors among nosocomial gram-positive and gram-negative bacteria, completion of these
aims will provide significant mechanistic insight into innovative counterstrategies to combat recalcitrant infections
by perturbing the biogenesis and turnover of hibernating ribosomes.

## Key facts

- **NIH application ID:** 10522119
- **Project number:** 2R01GM121359-06
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** M.-N. Frances Yap
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $336,891
- **Award type:** 2
- **Project period:** 2017-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522119

## Citation

> US National Institutes of Health, RePORTER application 10522119, Regulation and function of bacterial hibernating 100S ribosome (2R01GM121359-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10522119. Licensed CC0.

---

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