# The Role of the RNA-Binding Protein AUF1 in Idiopathic Pulmonary Fibrosis

> **NIH NIH F32** · UNIVERSITY OF MINNESOTA · 2020 · $34,414

## Abstract

Project Summary/Abstract
Idiopathic Pulmonary Fibrosis (IPF) is characterized by progressive fibrosis of the gas-exchange apparatus
leading to either death by asphyxiation or lung transplant. Currently there are two approved therapies to slow
the progression of IPF, but no therapies for halting the disease. Our work is focused on bridging the
knowledge gap regarding the molecular mechanisms of IPF progression, a prerequisite for developing
therapeutics that arrest the disease. Our lab, along with others in the field has identified a feed-forward loop in
IPF. When lung fibroblasts sense the fibrotic extracellular matrix (ECM) in IPF there is downregulation of the
microRNA biogenesis machinery component DICER1. This leads to decreased microRNA biogenesis,
including the master negative regulator of ECM genes, miR-29; which in turn results in increased ECM
deposition and progression of fibrosis. Expression of the DICER1 transcript is controlled post-transcriptionally
through binding by the RNA-binding protein AU-rich element binding factor 1 (AUF1), leading to rapid mRNA
decay. Our preliminary work has identified activation of the AUF1-DICER1 mRNA interaction in primary
human lung fibroblasts on IPF-ECM, leading us to ​hypothesize that ECM-dependent modulation of AUF1
function is a major mechanism for DICER1 suppression and the development of a fibrogenic
phenotype. In Aim 1, using primary human lung fibroblasts cultured on control ​versus IPF-ECM, we will
decipher the AUF1-DICER1 mRNA interaction followed by a genome wide-assessment of the AUF1
interactome. In aim 2, we test the hypothesis that AUF1 modulation is sufficient to confer a fibrotic phenotype
on an otherwise normal primary human lung fibroblast using two xenograft models: 1) Gain and loss of AUF1
function in our previously published zebrafish embryo xenograft model and 2) Gain of AUF1 function in a
mouse xenograft model. Through completion of these experiments under the mentorship of Dr. Peter
Bitterman, and the training plan outlined in the attached documents, I will be well prepared to pursue the next
steps toward a career as an independent pediatric physician-scientist.

## Key facts

- **NIH application ID:** 9933818
- **Project number:** 5F32HL145988-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Daniel J Beisang
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,414
- **Award type:** 5
- **Project period:** 2019-02-18 → 2020-07-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933818

## Citation

> US National Institutes of Health, RePORTER application 9933818, The Role of the RNA-Binding Protein AUF1 in Idiopathic Pulmonary Fibrosis (5F32HL145988-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933818. Licensed CC0.

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