# Mechanism and regulation of nuclear RNA export

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $438,739

## Abstract

ABSTRACT
Nuclear mRNA export is a fundamental component of the gene expression program in eukaryotes and is
intimately linked to upstream (transcription and nuclear RNA surveillance) and downstream (translation and
cytoplasmic RNA decay) events. Within my group, we study the mechanisms by which the fate (nuclear export
vs. decay) of an mRNA-protein complex (mRNP) is determined and regulated. Current studies within the lab
focus on understanding how RNA-binding protein (RBP) constituents of an mRNP direct nuclear RNA processing
and export, including interactions with the nuclear pore complex (NPC). Recent efforts in my group have led to
the discovery of a novel function for the mRNA export factor Dbp5 in tRNA export and the SR-like protein Npl3
in the meiotic splicing regulatory network. In addition, we have characterized mutation-induced alterations in
polyadenylation that promote imbalances in the distribution of RBPs between mRNA and non-coding (nc)RNA
processes and the loss of nuclear RNA processing homeostasis. At the core of these events is the mRNP, which
remains ill-defined in terms of how changes in mRNP architecture, including gain or loss of specific RBPs, directs
distinct transcript fates, including mRNA export. Consequently, our goals over the next five years focus on a
quantitative interrogation of mRNP biology, encompassing function, regulation, and structure. Pursuing this goal
is timely given the newly amassed knowledge of RBPs central to both mRNA and ncRNA biology, the
technologies available to apply these questions, and the need to understand how disease states arise in the
context of mutations within conserved RBP components or their modulation by viruses. A critical factor in mRNA
export is Dbp5 (DDX19 in humans), a highly conserved DEAD-box protein (DBP) that mediates directional mRNP
export through NPCs via modulation of RNA-protein interactions. Dbp5 is activated by the NPC component Gle1-
InsP6, which we have also shown to be required for tRNA export, in addition to the known role of Gle1 in mRNA
export. Questions that must be addressed to close major knowledge gaps in the RNA export field include: (1)
How is mRNP composition regulated to achieve directional transport through NPCs? (2) Are mRNA and ncRNA
export pathways integrated or distinct? (3) Is there coordination of RNA processing and export via shared RBPs
between mRNPs and ncRNPs? By addressing these questions, we expect to provide a molecular framework
that describes how Dbp5 and other RBPs engage, modify, and direct nuclear RNA processing and export. These
data are essential to understanding the flux of RNPs through NPCs to match cellular demand and how altering
this process by mutation leads to disease. In addition, these results will contribute to the understanding and
methodology within the DEAD-box protein, RNA transport, and gene expression fields, thereby fundamentally
contributing to the study of RNA biology.

## Key facts

- **NIH application ID:** 10406491
- **Project number:** 1R35GM145328-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Benjamen H.W. Montpetit
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $438,739
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406491

## Citation

> US National Institutes of Health, RePORTER application 10406491, Mechanism and regulation of nuclear RNA export (1R35GM145328-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10406491. Licensed CC0.

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