# Maximizing Quantitative Structural Information from High-Throughput RNA Structure Probing

> **NIH NIH R03** · NORTHWESTERN UNIVERSITY · 2021 · $79,583

## Abstract

Project Summary
RNAs enact many diverse cellular functions which are often performed by specific RNA structures that mediate
interactions with cellular factors, coordinate regulatory events, or in some cases perform catalysis of central
biochemical reactions. RNA structure probing coupled to high-throughput sequencing is used to help determine
these structures and construct models of functional RNA folds. By measuring the reactivities of nucleotides in
an RNA to the chemical probes, properties of an RNA fold such as regions that are structured or unstructured
can be elucidated. However, at present, RNA structure probing suffers from many limitations, including a lack
of approaches that can be used to standardize measured experimental reactivities against extrinsic
experimental factors that contribute to measurement noise. Because of this, mostly ad hoc normalization
schemes have been used to account for these factors which has resulted in a limitation on our understanding
and interpretation of reactivities. In addition, these procedures cannot accurately standardize reactivities to a
defined and understood quantitative reactivity scale and therefore cause underlying intrinsic RNA structural
information to be lost. Our long-term goal is to address these existing limitations. Here we propose to
create an approach to standardizing experimentally determined RNA chemical probing reactivities to a
quantitatively defined scale that can be used to extract meaningful and reproducible data between
experiments and across labs. This standardization approach will allow a more quantitative understanding of
chemical probing reactivity to be developed that will improve downstream computational approaches that use
this data for RNA structural modeling. This approach will also allow for increased data sharing, understanding
and integration with complementary omics datasets that interrogate additional features of RNA biochemistry
beyond structure. As chemical probing is being increasingly used to address longstanding and new questions
about the role of RNA structure across the cell, we anticipate these developments to contribute to a deeper
understanding of RNA folding, RNA-protein interactions, RNA folding dynamics, shifts in the structural
populations of RNA, and even changes in structure due to RNA modifications.

## Key facts

- **NIH application ID:** 10149378
- **Project number:** 5R03HG011113-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Julius Beau Lucks
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,583
- **Award type:** 5
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149378

## Citation

> US National Institutes of Health, RePORTER application 10149378, Maximizing Quantitative Structural Information from High-Throughput RNA Structure Probing (5R03HG011113-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10149378. Licensed CC0.

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