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Updated: Nov 17, 2025
10:01
In vitro Methylation Assay to Study Protein Arginine Methylation
Published on: October 5, 2014
15.6K
The methyltransferase PRMT1 regulates γ-globin translation.
Ying Wang1, Xinyu Li2, Jingru Ge2
1State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing, China; Department of Urology, University of California, San Francisco, California, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
The Journal of Biological Chemistry
|February 15, 2021
Summary
Researchers found that PRMT1 suppresses fetal globin synthesis at the translational level by blocking a uORF. Inhibiting PRMT1 with furamidine dihydrochloride offers a potential new therapy for beta-hemoglobinopathies.
Area of Science:
- Molecular Biology
- Genetics
- Pharmacology
Background:
- Inducing fetal hemoglobin (HbF) is a therapeutic strategy for beta-hemoglobinopathies.
- Regulation of HbF at the translational level is not well understood.
- Stress signaling can induce HbF translationally but may suppress it transcriptionally.
Purpose of the Study:
- To identify mechanisms regulating fetal gamma-globin (γ-globin) translation.
- To explore the role of protein arginine methyltransferases (PRMTs) in γ-globin regulation.
- To discover novel therapeutic targets for beta-hemoglobinopathies.
Main Methods:
- Functional CRISPR screen targeting PRMTs in K562 cells.
- Analysis of γ-globin expression at transcriptional and translational levels.
- Identification of upstream open reading frames (uORFs) in the γ-globin 5' UTR.
- Pharmacological inhibition of PRMT1 using furamidine dihydrochloride.
Main Results:
- Several PRMTs were found to inhibit γ-globin transcription.
- PRMT1 specifically suppresses γ-globin synthesis translationally.
- A non-AUG uORF in the γ-globin 5' UTR acts as a translational barrier.
- PRMT1 deficiency bypasses this uORF, enhancing γ-globin translation.
- Furamidine dihydrochloride, a PRMT1 inhibitor, targets this suppression mechanism.
Conclusions:
- PRMT1 regulates γ-globin translation via a 5' UTR uORF.
- Targeting PRMT1 offers a novel therapeutic strategy for beta-hemoglobinopathies.
- This study reveals a new mechanism for controlling globin synthesis.
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