# Function and Regulation of a DEAD-box protein in mRNA Export

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $398,344

## Abstract

PROJECT SUMMARY
mRNA export is a fundamental component of the gene expression program in eukaryotes, which is tightly
linked to upstream (e.g. transcription) and downstream (e.g. RNA surveillance and translation) events.
Development of mRNA export models and an understanding of the role export plays in regulated gene
expression (e.g. biased export of select transcripts) requires a quantitative assessment of mRNA export that
encompasses kinetics and molecular mechanism. Pursuing this goal is timely given the knowledge that has
amassed and technology developed (e.g. RNA-aptamer tagging systems) and is vital to understanding how
disease arises in the context of perturbations to this cellular process. A key factor to consider is Dbp5p, a
DEAD-box protein (DBP) that plays a critical role in export by modulating RNA-protein interactions important to
directional transport of mRNAs through nuclear pore complexes (NPCs). Dbp5p is activated (i.e. enhanced
ATPase activity) by the NPC components Gle1p and Nup159p, and although the impact of these regulators
have been studied in vitro (e.g. steady-state kinetics and structural biology), the kinetic and thermodynamic
origins of this regulation, and how ATPase cycling influences spatial and temporal aspects of mRNA export in
vivo, remain unresolved. Therefore, a necessary step towards accurate models of mRNA export are a
quantitative understanding of (1) ATP utilization by Dbp5p and (2) the impact of Dbp5p on mRNA export
dynamics in vivo, including how these events are coupled to interactions with NPC regulatory factors.
Specifically, knowledge of the rate and equilibrium constants dictating Dbp5p ATPase activity and interactions
with Nup159p and Gle1p is necessary for developing predictive NPC transport models that can be combined
with measurements of mRNA export kinetics and efficiency in vivo. Proposed research efforts in Aim 1 focus
on transient (pre-steady state) kinetic and quantitative equilibrium methods and analyses to determine how
Nup159p and Gle1p interact with and regulate Dbp5p. Aims 2 and 3 employ in vivo studies using single
particle RNA imaging and transcriptomic approaches to address spatial and temporal aspects of mRNA export,
including the role of Dbp5p, Gle1p and Nup159p in modulating export. To accomplish these aims, new
experimental and analysis methods readily applicable to other DBPs and RNA transport systems will be
developed. Completion of the proposed activities will establish a quantitative molecular framework that
describes how regulatory factors function to modulate Dbp5p ATPase activity and mRNA transport, which is
fundamental to gene expression, cell physiology, and disease pathology.
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## Key facts

- **NIH application ID:** 9928055
- **Project number:** 5R01GM124120-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Benjamen H.W. Montpetit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $398,344
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928055

## Citation

> US National Institutes of Health, RePORTER application 9928055, Function and Regulation of a DEAD-box protein in mRNA Export (5R01GM124120-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9928055. Licensed CC0.

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