# Molecular mechanisms of ribosome pausing and the cellular response

> **NIH NIH R37** · JOHNS HOPKINS UNIVERSITY · 2022 · $353,700

## Abstract

Protein synthesis is a highly conserved process in all kingdoms of life that can be broken down into four
distinct phases: initiation, elongation, termination and ribosome recycling. The broad goals of this
research program are to use biochemical and genomic approaches to shed light on the common and
distinctive molecular features of translation elongation, termination, and recycling in bacteria and
eukaryotes, and their control. Here we are particularly focused on one aspect of translational control in
which ribosomal stalling triggers a cellular response leading to mRNA decay, targeted proteolysis, and
ribosome recycling. In particular, we focused initially on a highly conserved stalling motif, the poly-basic
peptide sequence, that is of particular relevance in eukaryotic cells where alternative polyadenylation site
usage commonly leads to "non-stop" mRNAs. We will continue to use in vitro biochemistry and in vivo
ribosome profiling to look at the molecular mechanics of this biologically important and conserved process
(and other related systems). More specifically, we propose (1) to use our previously established in vitro
reconstituted translation system (with S. cerevisiae components) to ask a series of questions about
ribosome-based mechanisms for sensing translational perturbations, (2) to use a series of reporters in
yeast to screen for novel components that contribute to these mRNA surveillance pathways and (3) to use
ribosome profiling approaches to define the biologically relevant in vivo targets, their molecular features,
and the factors that contribute to these important pathways. We anticipate that the synergy of these
approaches will be powerful in defining biologically relevant mechanism.

## Key facts

- **NIH application ID:** 10474374
- **Project number:** 5R37GM059425-22
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RACHEL GREEN
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $353,700
- **Award type:** 5
- **Project period:** 1999-05-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474374

## Citation

> US National Institutes of Health, RePORTER application 10474374, Molecular mechanisms of ribosome pausing and the cellular response (5R37GM059425-22). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10474374. Licensed CC0.

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