# Causes and consequences of differential mRNA localization to mRNP granules

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $381,934

## Abstract

Project Summary/Abstract
A conserved mechanism of gene regulation during stress is the phase separation of mRNA and
proteins into membrane-less compartments termed messenger ribonucleoprotein (mRNP) granules.
Recent research has implicated aberrant formation of these granules in the pathology of a variety of
neurodegenerative diseases. It has been proposed that mislocalization of mRNAs and proteins to these
pathological inclusions can cause a toxic gain-of-function through altered gene expression control. Our
research program aims to use the formation of mRNP granules during glucose starvation in yeast to
elucidate basic mechanistic principles about the formation and function of these membrane-less
compartments as well as to apply the knowledge and technical expertise from yeast to understand how
phase separation of RNA-binding proteins associated with neurodegenerative diseases impinge upon
gene expression in mammalian cells. This research builds on our discovery that during stress,
transcription and translation can be coupled, as promoter elements can determine the localization of
mRNAs to mRNP granules, thereby impinging on their subsequent translatability. Our strategy will take
a two-part approach. The first direction will focus on elucidating the mechanism by which promoter
elements in the nucleus can direct the localization of mRNAs to mRNP granules in the cytoplasm.
Second, we will explore the function that this differential localization has on the gene expression of
yeast and mammalian cells. This research will give insight into basic questions of what specifies mRNA
localization to membrane-less compartments and how this affects the gene expression of the cell,
which is important for understanding the effects that toxic mRNP aggregates may have on cells during
neurodegeneration.

## Key facts

- **NIH application ID:** 10201656
- **Project number:** 5R35GM128798-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Brian Matthew Zid
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,934
- **Award type:** 5
- **Project period:** 2018-07-25 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201656

## Citation

> US National Institutes of Health, RePORTER application 10201656, Causes and consequences of differential mRNA localization to mRNP granules (5R35GM128798-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201656. Licensed CC0.

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