# Decoding the RNA Structurome: Method Development and Function Analysis

> **NIH NIH R00** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $31,119

## Abstract

Project Summary
 The long-term goal of my research is to comprehensively characterize the RNA structurome, here
defined as the collection of all RNA structures and RNA-RNA interactions in living cells. RNA structures
represent an important, yet under-appreciated, layer of genetic information that is essential for the
interpretation and execution of the genomic blueprint. In this application for career development award, I have
outlined research strategies that range from development of methods for RNA structure determination to
functional characterization of RNA structures, which will eventually lead to applications to human diseases, the
ultimate goal of genome medicine.
 RNA structures and interactions are fundamental to RNA's diverse functions, such as guiding,
scaffolding and catalysis. Not surprisingly, genetic alternations of RNA structures or helicases (enzymes that
remodel RNA structures) underlie many human diseases, including various cancers. RNA viruses cause some
of the most deadly human infections, and viral genomic RNA structures control critical steps in their lifecycle.
However, only a few RNA structures have been determined due to lack of proper methods. To address this
issue, I developed PARIS, a psoralen-crosslinking based method for high throughput mapping of RNA
duplexes in living cells at single-molecule level with near base-pair resolution (Lu et al. 2016 Cell).
 In this proposal, I will further increase the capabilities of PARIS by developing new high-efficiency
photochemical crosslinkers (high solubility psoralens and bifunctional carbazoles) and resolution-refining
enzymatic strategies. PARIS-determined structures made it possible to conduct global screens for their
functions using synthetic translation reporters. Systematic mutagenesis and screening of protein effectors will
be used to dissect the mechanism of function for regulatory structural elements.
 In summary, the proposed studies will deliver a set of powerful tools to the broad RNA community for
RNA structure determination, and provide new insights into RNA functions through multi-scale interrogation of
RNA structures, from domains to single base pairs. Comprehensive characterization of the RNA structurome
will uncover the regulatory mechanisms that translate the genome to phenotype, in both physiological and
disease contexts.

## Key facts

- **NIH application ID:** 10129051
- **Project number:** 3R00HG009662-04S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Zhipeng Lu
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,119
- **Award type:** 3
- **Project period:** 2018-12-17 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129051

## Citation

> US National Institutes of Health, RePORTER application 10129051, Decoding the RNA Structurome: Method Development and Function Analysis (3R00HG009662-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10129051. Licensed CC0.

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