ArticleMolecular therapy. Nucleic acids2025
Enhancing mRNA translation efficiency by introducing sequence optimized AU-rich elements in 3' UTR via HuR anchorage.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- Transgene sequence codon optimization and composition determines replication competence of self-amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Characterizing highly conserved fragments in 3'UTRs via statistical and transfer learning approaches.NAR genomics and bioinformatics · 2026Article
- RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine.International journal of molecular sciences · 2026Review
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Risk model based on adenylate uridylate (AU)-rich elements genes for assessing esophageal cancer prognosis and immune landscape.Journal of thoracic disease · 2026Article
- A protocol for computational design of mRNA vaccines with high functionality and specificity.Biology direct · 2026Article
- Enhancement of Therapeutic mRNA Translation in Cellular Stress Conditions.International journal of molecular sciences · 2026Review
- STOML2 promotes hepatocellular carcinoma cell proliferation, invasion and migration by activating the PI3K/AKT signaling pathway (Review).Oncology letters · 2026Review
- mRNA-engineered CRISPR-Cas epigenetic editors enable durable and efficient gene silencingInnovation (Cambridge (Mass.)) · 2026Article
- m6A-Modified Nucleotide Bases Improve Translation of In Vitro-Transcribed Chimeric Antigen Receptor (CAR) mRNA in T Cells.International journal of molecular sciences · 2026Article
- mRNA therapeutics: Transforming medicine through innovation in design, delivery, and disease treatment.Molecular therapy. Nucleic acids · 2025Review
- Engineering bone tissue with mRNA: from molecular design and delivery to clinical applications.Materials today (Kidlington, England) · 2025Article
- Airway-applied mRNA vaccine needs tailored sequence design and high standard purification that removes devastating dsRNA contaminant.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- RNA binding protein HuR regulated by OIP5-AS1 may be involved in maternal transcript degradation during the human maternal-to-zygotic transition.BMC genomics · 2025Article
- We ARE boosting translation: AU-rich elements for enhanced therapeutic mRNA translation.Molecular therapy. Nucleic acids · 2025Article
- Differential regulatory role of AU-rich and GU-rich elements inFrontiers in microbiology · 2025Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mRNA technology holds immense promise as an innovative therapeutic approach with applications spanning infectious disease vaccines, cancer immunotherapy, protein replacement, and gene editing. However, practical use of mRNA has been hindered by challenges such as low cellular stability and transient protein expression. For addressing these, we propose a novel strategy to optimize mRNA sequences, particularly in the untranslated region, by inserting adenylate/uridylate-rich elements (AU-rich elements) to enhance stability and protein expression. Our investigation revealed that integrating AU-rich elements between the open reading frame (ORF) and the 3' untranslated region (3' UTR) significantly enhances RNA stability compared with other insertion sites. We identified cytoplasmic Human antigen R (HuR) as an essential RNA-binding protein responsible for promoting mRNA stability and translation, confirmed through HuR knockdown experiments and pull-down assays between AU-rich elements and HuR. Through rational design, we optimized the sequence of natural AU-rich elements and identified the essential "AUUUA" element, which, with certain repeats, can increase protein expression up to 5-fold. To demonstrate the universality of AU-rich element sequences in enhancing mRNA translation, we switched the coding proteins from luciferase to EGFP, mCherry, and ovalbumin (OVA), finding that both natural and engineered AU-rich element sequences amplify the expression of these proteins. In conclusion, leveraging the functionalities of RNA-binding proteins and the natural regulation of RNA stability in the untranslated region represents a novel strategy to enhance mRNA pharmacokinetics in the cytoplasm, expanding the potential applications of mRNA in therapeutic drugs.
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