ArticleNucleic acids research2010
Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 388 papers.
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Who cites it
388 citing papers in PubMed, 658 citations in OpenAlex.
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- Quantum chemical profiling of the electronic structure and hydrolytic stability of modified ribonucleosides.Physical chemistry chemical physics : PCCP · 2026Article
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- Imaging and safety profiling of inhaled siRNA RyR2 in human respiratory models.Archives of toxicology · 2026Article
- Analytical Characterization and Stability Assessment of RNA-Based Vaccines.Pharmaceutics · 2026Review
- The impact of psuedouridine modification on human tRNA.Biochemical Society transactions · 2026Review
- To modify or not to modify: Rethinking mRNA design for CAR T cell engineering.Molecular therapy. Nucleic acids · 2026Article
- Engineered mRNA backbones for gene expression in human T cells.Molecular therapy. Nucleic acids · 2026Article
- Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Enhancement of Therapeutic mRNA Translation in Cellular Stress Conditions.International journal of molecular sciences · 2026Review
328 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Previous studies have shown that the translation level of in vitro transcribed messenger RNA (mRNA) is enhanced when its uridines are replaced with pseudouridines; however, the reason for this enhancement has not been identified. Here, we demonstrate that in vitro transcripts containing uridine activate RNA-dependent protein kinase (PKR), which then phosphorylates translation initiation factor 2-alpha (eIF-2α), and inhibits translation. In contrast, in vitro transcribed mRNAs containing pseudouridine activate PKR to a lesser degree, and translation of pseudouridine-containing mRNAs is not repressed. RNA pull-down assays demonstrate that mRNA containing uridine is bound by PKR more efficiently than mRNA with pseudouridine. Finally, the role of PKR is validated by showing that pseudouridine- and uridine-containing RNAs were translated equally in PKR knockout cells. These results indicate that the enhanced translation of mRNAs containing pseudouridine, compared to those containing uridine, is mediated by decreased activation of PKR.
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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.