# ncRNA: Structure, Interactions and Inhibition

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2020 · $630,830

## Abstract

Project Summary/Abstract
This project studies the structural principles underlying the biological function of non-
coding RNAs and investigates new approaches to inhibiting their function in disease. It
studies how these transcripts fold; how they recognize other RNAs, RNA-binding proteins
and epigenetic enzymes; how functional SNPs correlated with cancer progression or
patient prognosis affect RNA structure and protein binding. It aims to develop engineered
proteins and peptide mimetics to inhibit ncRNA misfunction in human cancers.
 Its premise is that providing molecular mechanistic insight on ncRNA through
structure analysis and the establishment of structure-function relationships is one of the
most important current outstanding questions in molecular structural biology, because of
the enormous gap in knowledge created by the discovery that hundreds of thousands of
transcripts are actively transcribed. Furthermore, the widespread occurrence of functional
genetic variation in ncRNAs, and the association of mutation or mis-expression of
ncRNAs with disease outcome in patients underscore the biomedical importance of these
transcripts and reveal their potential therapeutic value. Molecular insight is necessary to
fully understand their biological function, frame hypotheses on how misregulation,
mutation or post-transcriptional modification causally lead to human disease, identify and
validate molecular targets and discover new chemistry for pharmacological intervention.
 These broad goals will be pursued through a multi-scale approach to establishing
the structure of ncRNAs, including the high resolution investigation of domains where
specific functions reside, and of their interaction with proteins and microRNAs. The project
will also pursue the further development of engineered proteins and peptide mimetics that
target functional domains of ncRNAs involved in malignant transformation. In collaboration
with cancer and developmental biologists, we will conduct experiments in primary cell lines
and model organisms to parallel our biochemical, biophysical and structural investigations,
and obtain cellular and organismal validation of the activity and mechanism of action of
new inhibitors.

## Key facts

- **NIH application ID:** 9899819
- **Project number:** 5R35GM126942-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Gabriele Varani
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $630,830
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899819

## Citation

> US National Institutes of Health, RePORTER application 9899819, ncRNA: Structure, Interactions and Inhibition (5R35GM126942-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899819. Licensed CC0.

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