# Iron-sensitive RNA regulation during erythropoiesis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $394,214

## Abstract

PROJECT SUMMARY
Proper erythropoiesis requires coordinated changes in gene expression and protein synthesis for stem and
progenitor cells to differentiate and amass the striking amount of iron-laden hemoglobin required to sustain life
in humans. Anemia—insufficient circulating erythrocytes—is most frequently caused by iron deficiency which
remains one the most common nutritional deficit in the world. Beyond hemoglobin production, the role of iron in
other cellular processes during erythropoiesis, such as gene expression and RNA processing is poorly
understood. RNA processing events are mediated by RNA binding proteins, such as the poly C binding proteins
(PCBPs). PCBP2 regulates erythropoiesis via alternative splicing of gene transcripts that drive erythroid
differentiation programs. Surprisingly, PCBPs were also discovered to function as intracellular iron chaperones,
raising the question of whether iron-binding occurs independently of or in concert with RNA-binding. Given that
iron levels intimately modulate red blood cell differentiation, we sought to investigate whether PCBP activity is
modulated by iron in the context of red cell development. Specifically, we hypothesize that iron modulates the
affinity or specificity of PCBPs towards target RNAs causing changes in RNA splicing that are important for red
blood cell differentiation. We will address this hypothesis by i) determining the effect of iron on PCBP-RNA
interactions using unbiased high throughput in vitro assays, ii) evaluating the effect of iron on PCBP-regulated
RNA splicing events in cells, and iii) determine global gene expression and RNA splicing changes in primary
human and mouse samples with and without iron deficiency. From these experiments we will uncover iron-
sensitive RNA splicing programs that dictate erythropoiesis.

## Key facts

- **NIH application ID:** 10397649
- **Project number:** 5R01DK124773-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Maria M. Aleman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,214
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397649

## Citation

> US National Institutes of Health, RePORTER application 10397649, Iron-sensitive RNA regulation during erythropoiesis (5R01DK124773-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10397649. Licensed CC0.

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