# Dynamically compartmentalized control of gene expression by messenger ribonucleoprotein granules

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $347,954

## Abstract

Project Summary
 Cells survive rapidly changing environments through adaptation mediated by sophisticated signaling
and gene regulatory processes. Posttranscriptional regulation by messenger ribonucleoprotein (mRNP)
granules plays an important role in the modulation of the proteome in response to environmental changes.
Processing bodies (PBs) and stress granules (SGs) are stress-induced mRNP granules, conserved from yeast
to mammals, that coordinate to regulate the localization, translation, degradation and storage of mRNAs.Given
their diverse effects on gene expression, PBs and SGs are implicated in many diseases, especially
neurodegenerative diseases and cancers. Although PBs/SGs are highly dynamic in nature, which proves
crucial for their functions, the majority of previous studies have focused only on the biochemical characteristics
of these granules with measurements made at static time points. How PBs/SGs are dynamically regulated and
their functional roles under physiological conditions remain largely unclear. Our recent results revealed that the
protein kinase A (PKA)-regulated formation of PBs and SGs plays a central role in regulating stress responsive
gene expression, promoting a long-lasting cellular memory to facilitate future stress adaptation. Building upon
these findings, we will combine experiments with modeling to systematically investigate how PBs/SGs process
dynamic inputs and control gene expression and long-term stress responses in yeast cells. In Aim 1, we will
track the dynamics of PBs/SGs, mRNAs, and proteins for representative stress responsive genes in single
cells in response to various dynamic environmental/signaling inputs. Based on these dynamic data, we will
develop a computational model to simulate and predict how PBs/SGs decode input dynamics and control the
mRNA fates and protein expression dynamics under rapidly changing environments. In Aim 2, we will track
inheritance of PBs/SGs from mother cells by their progenies over many generations using our recently-
developed yeast mother device, and will evaluate the role of granule inheritance in gene expression and stress
resistance in cell lineages. Using these data, we will construct a stochastic model to quantitatively evaluate the
contributions of mRNP granule inheritance to the heterogeneity across cell lineages and in clonal populations.
In Aim 3, we will systematically characterize the yeast proteome dynamics in response to environmental
changes and evaluate the roles of PBs and SGs in controlling these dynamics using a high-throughput "2K
DynOMICS" microfluidic platform. These data will be used to develop a systems-level dynamic model of gene
expression control by PBs/SGs. The completion of these aims will significantly advance our understanding
about how PBs/SGs operate and function under rapidly changing environments and will lead to the generation
of predictive models that will provide mechanistic insights into the PB/SG-mediated control of gene expressio...

## Key facts

- **NIH application ID:** 10188554
- **Project number:** 5R01GM111458-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Nan Hao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,954
- **Award type:** 5
- **Project period:** 2014-08-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188554

## Citation

> US National Institutes of Health, RePORTER application 10188554, Dynamically compartmentalized control of gene expression by messenger ribonucleoprotein granules (5R01GM111458-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10188554. Licensed CC0.

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