# Mechanisms of cotranscriptional RNA structure formation

> **NIH NIH R35** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $389,391

## Abstract

PROJECT SUMMARY
RNA folds into structures that perform fundamental cellular functions including gene regulation, the catalysis of
essential biochemical reactions, and genome defense. In cells, nascent RNA begins to fold when it emerges
from an RNA polymerase during transcription. Consequently, the direction and rate of transcription constrains
the structures that RNA can fold into, and nascent RNA molecules can interact directly with transcribing RNA
polymerases to control their own synthesis. Predicting how changes in the primary sequence of an RNA will
affect its structure and function therefore requires a mechanistic understanding of how RNA folding is
coordinated with transcription. Because all RNAs begin to fold cotranscriptionally, understanding how RNA folds
into functional secondary and tertiary structures will broadly impact our knowledge of RNA biology, the
development of RNA biotechnology, and our ability to identify and address human diseases that are caused by
RNA misfolding. However, probing the basic mechanisms of cotranscriptional RNA structure formation remains
challenging due to the lack of quantitative methods with sufficient throughput to address the complexity of RNA
folding processes. The proposed research will address this challenge by systematically dissecting
cotranscriptional RNA folding mechanisms using new tools that can assess how combinatorial sequence
perturbations affect RNA structure and function. The initial focus of these studies will be to understand how RNA
sequence composition and transcription kinetics coordinate the formation of RNA tertiary structures that enable
ligand-mediated transcription regulation by riboswitches. This work will uncover basic RNA folding principles that
enable accurate and efficient cotranscriptional RNA structure formation, which will advance our ability to both
engineer and characterize RNA systems for biomedical and biotechnological applications. More broadly, these
studies will establish a framework for investigating cotranscriptional RNA structure and function that, in the long
term, will contribute to a predictive understanding of how RNA folds and how sequence mutations can cause
RNA to fold into dysfunctional states.

## Key facts

- **NIH application ID:** 10499198
- **Project number:** 1R35GM147137-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Eric J Strobel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $389,391
- **Award type:** 1
- **Project period:** 2022-09-22 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499198

## Citation

> US National Institutes of Health, RePORTER application 10499198, Mechanisms of cotranscriptional RNA structure formation (1R35GM147137-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10499198. Licensed CC0.

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