# Stress Granules in Yeast and Mammals

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2021 · $313,600

## Abstract

PROJECT SUMMARY
 The goals of this grant are to understand the assembly, dynamics, and functions of stress
granules in the control of gene expression. Stress granules are cytoplasmic granules of untranslating
mRNAs and proteins that form when translation initiation is limiting. Stress granules are important for
three reasons. First, they sequester mRNAs and mRNA binding proteins and are thought to play a role in
regulating the translation or degradation of its resident mRNAs, particularly during stress. Second,
assemblies related to stress granules form in neurons and play a role in modulating synaptic plasticity
(McCann et al., 2011; Barbee et al., 2006). Thus, understanding stress granules will help to understand
other similar mRNP assemblies. Finally, aberrant stress granule accumulation appears to be a causative
event in a multisystem pathology, referred to as inclusion body myopathy (IBM) that includes
Amyotrophic Lateral Sclerosis (ALS), Frontotemporal lobar degeneration (FTLD), Paget's disease of
bone and some muscle myopathies. These diseases can be caused by mutations in RNA binding
proteins, such as hnRNPA1 or TDP-43, which increase stress granule assembly and amyloid formation,
or by mutations in the AAA-ATPase VCP, which decrease stress granule clearance. Moreover, these
diseases are characterized by the presence of cytoplasmic RNA-protein aggregates that contain markers
of stress granules. Given this importance in both normal stress responses and in pathological conditions,
an understanding of normal and aberrant stress granule formation and function is critical. In this grant,
we build on our recent analyses of the stress granule proteome and transcriptome to determine the effect
of stress granule formation on mRNA function, the mechanisms that target mRNAs to stress granules,
and the novel role of mRNA-mRNA interactions in trans on the assembly and maintenance of stress
granules. The specific questions addressed in this proposal are:
I) What is the impact of stress granule assembly on mRNA stability and decay?
II) What are the mechanisms of mRNA partitioning into stress granules?
III) What is the role of RNA-RNA interactions in stress granule assembly?
Completion of these aims will reveal fundamental principles of stress granule assembly and function,
including insights into how pathological RNP granules form and impact gene expression in affected
tissues.

## Key facts

- **NIH application ID:** 10119288
- **Project number:** 5R01GM045443-32
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** ROY PARKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,600
- **Award type:** 5
- **Project period:** 1991-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119288

## Citation

> US National Institutes of Health, RePORTER application 10119288, Stress Granules in Yeast and Mammals (5R01GM045443-32). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10119288. Licensed CC0.

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