# Finding, folding and characterizing the functions of disease-relevant RNA structures

> **NIH NIH R01** · IOWA STATE UNIVERSITY · 2020 · $360,307

## Abstract

PROJECT SUMMARY/ABSTRACT
Understanding the basic molecular details behind disease is a critical challenge for science. This proposal
aims to approach this by focusing on an understudied aspect of disease: the roles of RNA structure. The
overall goal of this project is to optimize a methodological pipeline to discover functional RNA elements in the
genomes of humans and their pathogens, deduce their structures, and characterize their functions. The end
objective is to gain a better understanding of how RNA structure is implicated in disease and to use this
information in novel ways to contribute toward improving human health: for example, by advancing RNA-based
therapeutic treatments. Over the course of this project we will optimize this pipeline by focusing on the infection
of human B cells by Epstein–Barr virus (EBV). EBV is a widespread human pathogen, which infects over 95%
of the adult population, and is implicated in a variety of cancers and autoimmune diseases. The mechanisms
behind EBV pathogenicity remain elusive and this proposal aims to focus on the roles of RNA and RNA
structure in infection and disease. Over the course of establishing lifelong latent infection, EBV both generates
its own RNAs and dysregulates various human RNAs. RNA plays a central role in human and pathogen
biology, forming the protein-coding and non-protein-coding molecules that are essential to gene expression.
RNA structure plays important regulatory roles: e.g. by mediating interactions or altering accessibility of
functional motifs. Thus, knowing the structure of RNA provides a great deal of biological knowledge and can be
used to deduce functional sequences from the genome. My previous work combined computational and
experimental approaches to discover RNA structures encoded within the EBV genome. This included a novel
class of viral RNAs, the stable intronic sequence (sis)RNAs, which I discovered. In this current proposal, we
follow up on the functional analyses of EBV-encoded RNAs and expand our focus to include human RNAs.
This will be accomplished by revisiting both genomes using innovative new approaches that we developed and
novel methods that are currently under development. This will be combined with genome-wide biochemical
structure analyses and functional assays performed in vitro (in cell-free systems) and within cultured human B
cells. The results of this proposal will be an enhanced basic understanding of how RNA and RNA structure is
involved in EBV infection and disease. There will be wider implications beyond EBV and its associated
pathologies: for example, part of our pipeline involves the analysis of conservation of RNA structure between
pathogens (potentially finding conserved mechanisms). As well, many discovered human motifs affected by
EBV will likely have functional roles in cancer and immunity; therefore, this proposal will provide general
insights into disease. These functional structures provide attractive targets for emerging RNA-targe...

## Key facts

- **NIH application ID:** 10018063
- **Project number:** 5R01GM133810-02
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Walter Moss
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $360,307
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018063

## Citation

> US National Institutes of Health, RePORTER application 10018063, Finding, folding and characterizing the functions of disease-relevant RNA structures (5R01GM133810-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10018063. Licensed CC0.

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