# Temporal coordination of stimulus-induced gene expression by RNA-binding proteins

> **NIH NIH R35** · UNIVERSITY OF COLORADO DENVER · 2022 · $388,750

## Abstract

SUMMARY
Cellular responses to external stimuli require dynamic gene regulation to facilitate rapid activation and effective
resolution. Although transcriptional responses are a textbook mechanism for stimulus-induced responses, post-
transcriptional regulation of mRNA translation and decay are the other side of the coin and are essential for rapid
and adaptable stimulus-induced responses. For example, immune activation generates a prototypical temporal
expression pattern for cytokine mRNAs known as an impulse response, which is a rapid pulse-like increase and
decrease in expression. The destabilization of cytokine mRNAs is required for proper resolution of the impulse
response and prevention of excess cytokine production. It is increasingly recognized that RNA-binding proteins
(RBPs) play critical roles in achieving an appropriate stimulus-induced gene expression response by regulating
RNA processing, decay, and translation of target RNAs. The over-arching goal of our research program is to
understand how RBPs temporally coordinate stimulus-induced gene expression and cellular phenotypes.
The model system we will use to study how dynamic RBP-RNA regulatory interactions temporally coordinate
stimulus-induced gene expression is human adrenal steroidogenesis. This is a classic ligand-induced system in
which the small peptide Angiotensin II (AngII) binds to its receptor in adrenal zona glomerulosa cells to stimulate
the production of aldosterone, the master regulator of blood pressure. Thus, tight control of regulatory timing is
required since it must be rapidly produced de novo from cholesterol in response to AngII. We have recently
demonstrated that AngII treatment of immortalized and primary adrenocortical cells results in an impulse
response. Furthermore, we found specific RBPs and regulated RNA decay facilitates the rapid implementation
and resolution of the AngII impulse response. In this proposal, we will test the hypothesis that MSI2 and ZFP36L2
are counteracting forces that, respectively, potentiate and attenuate the kinetics of stimulus-induced mRNA
levels by modulating target mRNA decay and translation, to ensure the proper timing and amplitude of the
impulse response. We will utilize cutting edge methods to gain temporal and quantitative insights into how
stimulus-induced changes in RBP binding determine changes in target mRNA expression responses and
ultimately cellular phenotype. The use of innovative approaches we use will help shift the field from a static to a
dynamic view of RBP-mRNA interactions and achieve mechanistic insight on how regulatory RBP-mRNA
interactions control mRNA fate decisions to govern cellular responses.

## Key facts

- **NIH application ID:** 10499530
- **Project number:** 1R35GM147025-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Neelanjan Mukherjee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499530

## Citation

> US National Institutes of Health, RePORTER application 10499530, Temporal coordination of stimulus-induced gene expression by RNA-binding proteins (1R35GM147025-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10499530. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*