ArticleNucleic acids research2022
Membrane-dependent relief of translation elongation arrest on pseudouridine- and N1-methyl-pseudouridine-modified mRNAs.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- NNature · 2026Article
- Cytoplasmic localization of pseudouridine synthase 7 facilitates a pseudouridine-dependent enhancement of cellular stress tolerance.Nature communications · 2026Article
- NNature · 2026Article
- Overcoming the eIF2α Brake in Human Cell-Derived Translation Systems.bioRxiv : the preprint server for biology · 2025Article
- Translation elongation: measurements and applications.RNA biology · 2025Review
- A novel plasmid-based co-tethered transcription platform for high yield, high purity mRNA synthesis.Nucleic acids research · 2025Article
- Advances in nanomaterials for enhancing cGAS-STING pathway mediated anti-tumor treatment.Materials today. Bio · 2025Review
- Cytoplasmic localization of PUS7 facilitates a pseudouridine-dependent enhancement of cellular stress tolerance.bioRxiv : the preprint server for biology · 2025Article
- A proximity-labeling-based approach to directly detect mRNA delivery to specific subcellular locations.Molecular therapy. Nucleic acids · 2025Article
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- A Luciferase-Based Approach for Functional Screening of 5' and 3' Untranslated Regions of the mRNA Component for mRNA Vaccines.Vaccines · 2025Article
- RNA modifications: emerging players in the regulation of reproduction and development.Acta biochimica et biophysica Sinica · 2024Review
- N1-methylpseudouridine modification level correlates with protein expression, immunogenicity, and stability of mRNA.MedComm · 2024Article
- N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation.Nature communications · 2024Article
- Comprehensive translational profiling and STE AI uncover rapid control of protein biosynthesis during cell stress.Nucleic acids research · 2024Article
- Deconvolution of synthetic mRNA expression: Nucleoside chemistry alters translatability.Bioengineering & translational medicine · 2024Article
- Exploring the Impact of mRNA Modifications on Translation Efficiency and Immune Tolerance to Self-Antigens.Vaccines · 2024Article
- RNA modification-mediated mRNA translation regulation in liver cancer: mechanisms and clinical perspectives.Nature reviews. Gastroenterology & hepatology · 2024Review
- A novel deep generative model for mRNA vaccine development: Designing 5' UTRs withActa pharmaceutica Sinica. B · 2024Article
- How snoRNAs can contribute to cancer at multiple levels.NAR cancer · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of therapeutically important proteins has benefited dramatically from the advent of chemically modified mRNAs that feature decreased lability and immunogenicity. This had a momentous effect on the rapid development of COVID-19 mRNA vaccines. Incorporation of the naturally occurring pseudouridine (Ψ) or N1-methyl-pseudouridine (N1mΨ) into in vitro transcribed mRNAs prevents the activation of unwanted immune responses by blocking eIF2α phosphorylation, which inhibits translation. Here, we report that Ψs in luciferase (Luc) mRNA exacerbate translation pausing in nuclease-untreated rabbit reticulocyte lysate (uRRL) and promote the formation of high-order-ribosome structures. The major deceleration of elongation occurs at the Ψ-rich nucleotides 1294-1326 of Ψ-Luc mRNA and results in premature termination of translation. The impairment of translation is mainly due to the shortage of membranous components. Supplementing uRRL with canine microsomal membranes (CMMs) relaxes the impediments to ribosome movement, resolves collided ribosomes, and greatly enhances full-size luciferase production. CMMs also strongly stimulated an extremely inefficient translation of N1mΨ-Luc mRNA in uRRL. Evidence is presented that translational pausing can promote membrane recruitment of polysomes with nascent polypeptides that lack a signal sequence. Our results highlight an underappreciated role of membrane binding to polysomes in the prevention of ribosome collision and premature release of nascent polypeptides.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.