# Mechanisms and Regulation of Nuclear mRNA Export

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2024 · $515,125

## Abstract

Project Summary
In all eukaryotic cells, export of mRNA from the nucleus to the cytoplasm is an essential step in gene
expression. As such, mRNA nuclear export is fundamental for all cellular activities and has been linked to
various diseases when it is dysregulated, such as in cancer, neurological disorders, and viral infections.
Our research focuses on elucidating the mechanisms and regulation of mRNA export under physiological
and pathological conditions. Within the nucleus, newly synthesized mRNAs are processed and packaged
with proteins to form ribonulceoprotein particles (mRNPs). The core machinery that facilitates the assembly
of export-competent mRNPs is the TREX (TRanscription/EXport) complex. Through the enzymatic activity
of its ATPase subunit Sub2/DDX39B, TREX facilitates loading of export-specific factors including the export
receptor NXF1•NXT1 to form export-competent mRNPs. We have recently elucidated the architecture of
the TREX complex and defined key steps of Sub2/DDX39B’s activity. These findings provide a solid
foundation for us moving forward to investigate fundamental aspects of mRNA export that remain poorly
understood. In this grant period, we aim to identify and structurally characterize the physical and functional
interaction network that connects different steps of mRNA export and coordinates the export process with
other nuclear events. We envision that these molecular connections spatiotemporally regulate the ATPase-
driven mRNP assembly and establish selective export of mature transcripts. The resulting biochemical and
structural knowledge will generate hypotheses that we will test at the cellular level. In addition, we aim to
investigate how viruses exploit host mRNA export to facilitate their replication. We recently have elucidated
the molecular basis for how influenza A virus and SARS-CoV-2 target NXF1•NXT1 to block host gene
expression. We will continue to study the various mechanisms that influenza A virus uses to exploit host
mRNA export factors. Together, our work will provide mechanistic insights into the mRNA export pathway
and may offer novel therapeutic opportunities for viral infections.

## Key facts

- **NIH application ID:** 10842003
- **Project number:** 2R35GM133743-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Yi Ren
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $515,125
- **Award type:** 2
- **Project period:** 2019-08-09 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842003

## Citation

> US National Institutes of Health, RePORTER application 10842003, Mechanisms and Regulation of Nuclear mRNA Export (2R35GM133743-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10842003. Licensed CC0.

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