# Project 2 - Nuclear Export and Translation

> **NIH NIH U54** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $434,287

## Abstract

Transport of HIV-1 RNAs from the nucleus and their regulated expression in the cytoplasm are critical steps of
the viral lifecycle. Domains present in viral RNA have been shown to regulate these events; namely, the export
of unspliced transcripts requires the Rev responsive element, RRE; alternative conformers of the 5'-leader
region dictate translation vs. packaging fates; and the recoding of genetic information that allows the
production of fixed ratios of viral proteins relies on the frameshifting signal. While elucidation of these RNA
structures, and thus mechanisms regulating these events, are closer to realization, studies carried out in CRNA
1.0 have established that both nuclear export and translational regulation are more multifaceted than
previously thought. Several major discoveries were not previously predicted or envisioned: the cytoplasmic
Gag:RRE interaction; the presence of transcriptional start site heterogeneity, and its consequence on
maintaining separate pools of 5'-leader structures; and the presence of a structural equilibrium between an
inactive stem-loop and an active, frameshift-permissive pseudoknot conformation. Based on these CRNA
discoveries, this project aims to gain a complete structural and mechanistic understanding of both nuclear
transport and translational regulation in HIV-1 by combining structural studies with visualization, biochemical
and virologic experiments. Our aims for understanding nuclear export will be to determine the high resolution
structures of the RRE nuclear export signal, the biological significance of Gag:RRE interactions, and the
nuclear export properties of various HIV-1 RNAs. Our aims for understanding translational regulation will be to
determine structures for the monomeric and the spliced env mRNA forms of the 5'-leader, and the structures
involved in the process of programmed ribosomal frameshifting.

## Key facts

- **NIH application ID:** 10245115
- **Project number:** 5U54AI150470-10
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Victoria Manuel D'Souza
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $434,287
- **Award type:** 5
- **Project period:** 2012-09-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245115

## Citation

> US National Institutes of Health, RePORTER application 10245115, Project 2 - Nuclear Export and Translation (5U54AI150470-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10245115. Licensed CC0.

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