# New Tools to Decipher the Role of lncRNAs and Their Protein Interactomes in Hematopoiesis

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $432,744

## Abstract

Project Summary/Abstract
Bioanalytical tools to study long noncoding RNAs (lncRNAs) and their protein interactors are desperately
needed. lncRNAs are critical elements in the transcriptional regulation of gene expression. They have been
shown to function through several different mechanisms. They may serve directly as gene-regulatory factors,
produced by transcription at the genomic site where they act. Alternatively, lncRNAs interact with proteins to
control gene expression. For example, lncRNAs can act as a “molecular sink” for proteins that interact with
DNA or RNA; in this case, binding of the protein to the lncRNA competes with its interaction with its primary
target. lncRNAs can also guide proteins to their DNA targets to either repress or activate transcription. They
can act not only in cis, or near their site of transcription, but also in trans, at multiple genomic sites. Finally,
lncRNAs can act as platforms upon which molecules can convene to perform a function as a team at a specific
location and time (e.g. histone modification complexes). Each of these mechanisms requires the interaction of
lncRNAs with a diverse protein cohort. Knowledge of the proteins bound to specific lncRNAs is thus essential
information needed to understand mechanisms by which lncRNAs control gene expression. Unraveling this
tremendous diversity of interactions demands tools capable of rapid identification and quantification of lncRNA-
associated proteins. Despite the great importance of lncRNAs and the proteins that interact with them, there
are significant limitations in the tools available to study them. We propose to develop and validate a suite of
powerful new tools for the discovery, identification, and quantification of lncRNAs and for the comprehensive
proteomic analysis of their protein interactomes.
It is known that lncRNAs direct gene expression to modulate cell fate in the hematopoietic system, enabling
diversification of gene programming during development. Disrupted lncRNA function can also contribute to
malignant transformation in specific myeloid and lymphoid cancers. GATA factor-regulated lncRNAs,
discovered in powerful genetic systems (wild type and Gata2 enhancer-mutant mice, GATA-1 genetic
complementation system and GATA factor knockdowns in primary human erythroid precursor cells), control
human erythroid precursor cell function and erythrocyte development. In initial profiling studies, we have
identified 74 GATA factor-regulated lncRNAs. The performance of the new tools developed here will be
thoroughly tested on a subset of these 74 lncRNAs to discover GATA factor-dependent regulatory circuits and
networks that control hematopoiesis.
The proposed research will drive state-of-the-art lncRNA identification and proteomic analysis of the lncRNA
interactome, applied to one of the most important regulatory networks in hematopoiesis. We will bring a new
and unprecedented level of visibility to the definition of the GATA factor-relevant lncRNA int...

## Key facts

- **NIH application ID:** 9861594
- **Project number:** 1R01HL149966-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Emery H. Bresnick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,744
- **Award type:** 1
- **Project period:** 2020-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861594

## Citation

> US National Institutes of Health, RePORTER application 9861594, New Tools to Decipher the Role of lncRNAs and Their Protein Interactomes in Hematopoiesis (1R01HL149966-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9861594. Licensed CC0.

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