# Studies of mRNA translational regulations in erythropoiesis

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2021 · $397,500

## Abstract

PROJECT SUMMARY
The goal of this study is to understand how mRNA translational control regulates the terminal differentiation of
erythroid cells under both normal and pathological conditions. Erythropoiesis, the production of red blood cells,
is essential to mammals. Malfunction of this cell differentiation process can cause severe anemias and is
associated with a large number of human hematological disorders, including many bone marrow failure
syndromes such as the myelodysplastic syndrome. Thus, characterizing the molecular mechanisms controlling
erythropoiesis is of both biological and clinical significance. Previous studies have characterized many
transcriptional regulatory networks controlling the erythroid cell differentiation. In addition, the transcriptomic
dynamics during erythropoiesis have been extensively surveyed. How these RNA changes are “read” and
interpreted by the translational apparatus, the ribosome, in the differentiating erythroid cells to generate proper
amounts of proteins, however, is still largely unknown. Recently, we uncovered widespread regulations of
protein synthesis during terminal erythropoiesis by parallel RNA and ribosome profiling on primary erythroid
cells at different developmental stages. Specifically, during terminal erythropoiesis, we identified hundreds of
differentially translated mRNAs, and their 3' untranslated regions have significantly enriched binding motifs of
several erythroid-specific RNA-binding proteins, implying translational regulatory networks. Moreover, we
found novel forms of translational regulations including dynamic usage of upstream open reading frames,
alternative translation terminations, and stoichiometric synthesis of multi-subunit complexes. These results
strongly argue for critical roles of dynamic translational control in erythropoiesis. Interestingly, mutations in
several components of the cellular translational apparatus, the ribosome, can cause several human genetic
diseases with manifestations of ineffective erythropoiesis, such as the Diamond-Blackfan anemia and the 5q-
syndrome. These clinical observations highlight the importance of studying translational regulations in erythroid
cell differentiation. In this study, we will: a) characterize the translational regulatory networks mediated by key
erythroid-specific RNA-binding proteins in normal erythropoiesis; b) determine how disease-associated
ribosomal protein mutations alter mRNA translation in erythroid cells. The results from this study will not only fill
an important knowledge gap in erythropoiesis, but also will provide important molecular insights into
ribosomopathies and potentially identify therapeutic targets for these human diseases.

## Key facts

- **NIH application ID:** 10181022
- **Project number:** 5R01HL141112-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Wenqian Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,500
- **Award type:** 5
- **Project period:** 2018-08-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10181022

## Citation

> US National Institutes of Health, RePORTER application 10181022, Studies of mRNA translational regulations in erythropoiesis (5R01HL141112-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10181022. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*