# Mechanisms of large non-coding RNA regulation of gene expression

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $249,000

## Abstract

PROJECT SUMMARY
Large non-coding RNAs (lncRNAs) comprise a newly recognized class of thousands of functional RNA
molecules that play important roles in a wide variety of cellular pathways. These lncRNAs can have significant
effects on gene expression, and are involved in controlling regulatory networks critical for cellular growth and
differentiation. Many lncRNAs are important players in human diseases, especially human cancers. An
emerging hypothesis is that lncRNAs regulate gene expression and cellular function by binding
functional protein complexes to organize and coordinate their activities. However, a main challenge in
understanding the mechanisms of lncRNA-mediated regulation of gene expression and cellular function has
been a lack of knowledge of their protein interaction partners. To address this research bottleneck, I have
developed a method to comprehensively define the proteins that directly interact with a lncRNA, termed RNA
Antisense Purification with Mass Spectrometry (RAP-MS). This method has so far been highly successful in
identifying direct and specific interaction partners of several cellular RNAs, including Xist lncRNA, 18S
ribosomal RNA, U1 small nuclear RNA, and 45S pre-ribosomal RNA. In the proposed work I will use RAP-MS
to identify the functional protein interactors of three lncRNAs (Tsix, Neat1, and Malat1) then identify the
interacting regions of lncRNAs and proteins and create detailed high resolution structural models of lncRNA
and protein complexes. Dissection of the sequence determinants of lncRNA-protein interactions at the level of
nucleotide and amino acid interactions will lead to an improved understanding of the mechanisms of action of
lncRNAs in controlling gene expression and regulating cellular function at a molecular level. The goals of this
study are to identify direct and specific lncRNA-interacting proteins using RAP-MS (Aim 1), determine
the functions of lncRNA-interacting proteins (Aim 2), and dissect the molecular structure of lncRNA-
protein complexes (Aim 3). Taken together, the results of these experiments will reveal how lncRNAs bind
and coordinate proteins into higher-order complexes to achieve their roles in regulating gene expression and
cellular function. An understanding of functional lncRNA-protein interactions at the level of amino acid and
nucleotide interactions will provide insight into the mechanisms of action of lncRNAs and reveal molecular
principles guiding lncRNA-protein assembly. In addition, identification of the underlying principles of lncRNA-
protein function at a detailed molecular level will lead to new opportunities to control and manipulate the action
of non-coding RNAs in mammalian cells during the initiation and progression of cancer and other disease
processes.

## Key facts

- **NIH application ID:** 9841944
- **Project number:** 5R00GM120494-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Colleen Adare McHugh
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841944

## Citation

> US National Institutes of Health, RePORTER application 9841944, Mechanisms of large non-coding RNA regulation of gene expression (5R00GM120494-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9841944. Licensed CC0.

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