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The success of using pseudouridine (Ψ) and its methylation derivative in mRNA vaccines against SARS-CoV-2 has sparked a renewed interest in this RNA modification, known as the 'fifth nucleotide' of RNA. In this Review, we discuss the emerging functions of pseudouridylation in gene regulation, focusing on how pseudouridine in mRNA, tRNA and ribosomal RNA (rRNA) regulates translation. We also discuss the effects of pseudouridylation on RNA secondary structure, pre-mRNA splicing, and in vitro mRNA stability. In addition to nuclear-genome-encoded RNAs, pseudouridine is also present in mitochondria-encoded rRNA, mRNA and tRNA, where it has different distributions and functions compared with their nuclear counterparts. We then discuss the therapeutic potential of programmable pseudouridylation and mRNA vaccine optimization through pseudouridylation. Lastly, we briefly describe the latest quantitative pseudouridine detection methods. We posit that pseudouridine is a highly promising modification that merits further epitranscriptomics investigation and therapeutic application.
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http://dx.doi.org/10.1038/s41580-025-00852-1 | DOI Listing |
Carbohydr Polym
November 2025
Department of Pharmaceutics, Parul Institute of Pharmacy, Faculty of Pharmacy, Parul University, Waghodia, Vadodara, 391760, Gujarat, India; Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India; Faculty of Pharmacy, Silpakorn Univers
As a diverse natural polymer called Chitosan, it created ground-breaking advancements in nucleic acid therapeutic delivery techniques for handling essential DNA and RNA delivery hurdles. The article investigates how nucleic acids form stable polyplexes with chitosan through electrostatic bonds, as well as explores their chemical and biological properties. The review explores how molecular weight, combined with the degree of deacetylation, combined with advanced functionalization strategies, help enhance delivery results.
View Article and Find Full Text PDFPlant J
September 2025
Institute of Molecular Biology, University of Oregon, Eugene, Oregon, 97403, USA.
Translation of the chloroplast psbA mRNA in angiosperms is activated by photodamage of its gene product, the D1 subunit of photosystem II (PSII), providing nascent D1 for PSII repair. The involvement of chlorophyll in the regulatory mechanism has been suggested due to the regulatory roles of proteins proposed to mediate chlorophyll/D1 transactions and the fact that chlorophyll is synthesized only in the light in angiosperms. We used ribosome profiling and RNA-seq to address whether the effects of light on chloroplast translation are conserved in the liverwort Marchantia (Marchantia polymorpha), which synthesizes chlorophyll in both the dark and the light.
View Article and Find Full Text PDFMetastasis is the leading cause of cancer related deaths, however therapies specifically targeting metastasis are lacking and remain a dire therapeutic need in the clinic. Metastasis is a highly inefficient process that is inhibited by extracellular stress. Therefore, metastasizing cells that ultimately survive and successfully colonize distant organs must undergo molecular rewiring to mitigate stress.
View Article and Find Full Text PDFNat Struct Mol Biol
September 2025
Department of Biochemistry 1, Theodor Boveri-Institute, University of Würzburg, Würzburg, Germany.
Transfer RNAs (tRNAs) are widely recognized for their role in translation. Here, we describe a previously unidentified function of tRNA as an assembly chaperone. During poxviral infection, tRNA lacking the anticodon mcmsU34 modification is specifically sequestered from the cellular tRNA pool to promote formation of a multisubunit poxviral RNA polymerase complex (vRNAP).
View Article and Find Full Text PDFJ Mol Biol
September 2025
Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Molecular, Cell, and Cancer Biology
Transfer RNAs (tRNAs) are subject to various chemical modifications that influence their stability or function. Adenosine to Inosine (A-to-I) editing in the tRNA anticodon at position A34 is an important modification that expands anticodon-codon recognition at the wobble position and is required for normal mRNA translation. The relevance of tRNA editing in cancer remains unexplored.
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