# Project 1 - Nuclear Gene Expression

> **NIH NIH U54** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $358,793

## Abstract

The long-term goal of this Program is to understand the molecular mechanisms that regulate HIV-1 nuclear
gene expression and to use this knowledge as a springboard to identify novel targets for therapeutic
intervention. A major barrier in HIV-1 biology is that many of the RNA structures and protein-RNA interactions
that regulate gene expression in the nucleus are unknown. These processes appear to be combinatorial in
nature, and thus systems-level approaches must be combined with functional biochemistry in order to elucidate
molecular events that determine patterns of HIV-1 gene expression. Our team (Al-Hashimi, Bieniasz, Cullen,
Hargrove, Kutluay, Rouskin, Swanstrom and Tolbert) will use cross-disciplinary expertise in virology,
chemical biology and structural biophysics to determine mechanisms of splicing and transcriptional control. We
will build on the successes of CRNA 1.0 that include: 1) mapping for the first time binding sites of specific
splicing regulatory proteins on the HIV-1 genome; 2) quantitation of the HIV-1 alternative splicing using a novel
next generation sequencing platform; 3) identification of novel cis RNA elements that control HIV-1 splicing and
4) determination of the 3D structures of novel HIV-1 RNA splicing elements both free and bound to a regulatory
protein. Motivated by these new discoveries, this project will overcome critical barriers that have stymied
pursuit of the understanding of HIV-1 splicing regulation. In CRNA 2.0, we will A) reveal how regulatory protein
factors and RNA elements cross talk to establish HIV-1 splicing patterns; B) elucidate 3D structures of RNA
and protein-RNA complexes that regulate HIV-1 splicing; C) determine the mechanisms by which RNA
structure affects splicing; and D) develop novel strategies to target HIV-1 RNA with small molecule inhibitors.

## Key facts

- **NIH application ID:** 9993266
- **Project number:** 5U54AI150470-09
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Blanton Smith Tolbert
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,793
- **Award type:** 5
- **Project period:** 2012-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993266

## Citation

> US National Institutes of Health, RePORTER application 9993266, Project 1 - Nuclear Gene Expression (5U54AI150470-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993266. Licensed CC0.

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