# Elucidating the structure-function relationship of LARP6-mediated collagen mRNA transport

> **NIH NIH P20** · BOISE STATE UNIVERSITY · 2022 · $207,135

## Abstract

PROJECT SUMMARY- Warner
Fibroproliferative diseases, such as pulmonary fibrosis, systemic sclerosis, liver cirrhosis,
cardiovascular disease, progressive kidney disease, and macular degeneration, to name a few,
are a leading cause of morbidity and mortality in the world and can affect all tissues and organ
systems. A key step in the synthesis of collagen is the transport of mRNA from the nucleus to
the endoplasmic reticulum, where it is translated, hydroxylated, and eventually exported to the
cell membrane through interactions with multiple chaperone proteins. Intercepting the mRNA
molecule from the nucleus, or stopping transport of mutant collagen mRNA to the ER could
provide a targeted therapy in cases of excessive or inappropriate collagen synthesis. Our long-
term goal is to understand the role that LARP6 plays in transport of collagen mRNAs so that we
can target this interaction to prevent fibrotic disease progression. The overall objective of this
proposal is to understand the molecular mechanisms that drive LARP6/mRNA interactions. Our
central hypothesis is that LARP6 utilizes conformational selection in the recognition and
discrimination of collagen mRNAs. We further hypothesize that dynamic sampling of the tandem
arrangement of the La and RRM domains allows LARP6 to accommodate a diverse set of
mRNA ligands. A logical extension of this hypothesis is that mRNA ligands also may also have
adapted structure and/or dynamics that in turn guide selection by LARP6. An understanding of
LARP6-mediated mRNA transport will lead to the identification of novel therapeutic targets that
can mitigate fibroproliferative disease.

## Key facts

- **NIH application ID:** 10415178
- **Project number:** 5P20GM109095-09
- **Recipient organization:** BOISE STATE UNIVERSITY
- **Principal Investigator:** Lisa R Warner
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $207,135
- **Award type:** 5
- **Project period:** 2014-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415178

## Citation

> US National Institutes of Health, RePORTER application 10415178, Elucidating the structure-function relationship of LARP6-mediated collagen mRNA transport (5P20GM109095-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10415178. Licensed CC0.

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