Wednesday, December 17, 2025 12/17/2025

Studies of mRNA translational regulations in erythropoiesis

Award Number: R01HL141112
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/30/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Studies of mRNA translational regulations in erythropoiesis - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2022	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	000	5	12/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	000	5	4/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $397,500 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	000	5	6/10/2022	NON-COMPETING CONTINUATION	$397,500
														Subtotal = $397,500

Issue Date FY: 2021 ( Subtotal = $397,500 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	000	4	5/25/2021	NON-COMPETING CONTINUATION	$397,500
														Subtotal = $397,500

Issue Date FY: 2020 ( Subtotal = $397,500 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	000	3	6/4/2020	NON-COMPETING CONTINUATION	$397,500
														Subtotal = $397,500

Issue Date FY: 2019 ( Subtotal = $397,500 )
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	001	2	5/24/2019	NON-COMPETING CONTINUATION	$397,500
2019	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	000	1	11/30/2018	NEW	$0
														Subtotal = $397,500

Issue Date FY: 2018 ( Subtotal = $397,500 )
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Blood Diseases and Resources Research	000	1	8/30/2018	NEW	$397,500
														Subtotal = $397,500

Grand Total All Awards = $1,987,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Studies of mRNA translational regulations in erythropoiesis

Award Number: R01HL141112

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/30/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer