# Regulation and function of bacterial 100S ribosome - Admin Equip Supplement on R01GM121359-07

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $41,338

## Abstract

PROJECT SUMMARY (from the parent award)
 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 In our unpublished work, we isolated an additional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 extra-
ribosomal 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:** 11098263
- **Project number:** 3R01GM121359-08S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** M.-N. Frances Yap
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,338
- **Award type:** 3
- **Project period:** 2017-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098263

## Citation

> US National Institutes of Health, RePORTER application 11098263, Regulation and function of bacterial 100S ribosome - Admin Equip Supplement on R01GM121359-07 (3R01GM121359-08S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11098263. Licensed CC0.

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