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The pseudouridylase Pus1 catalyzes pseudouridine (Ψ) formation at multiple uridine residues in tRNAs, and in some snRNAs and mRNAs. Although Pus1 is highly conserved, and mutations are associated with human disease, little is known about eukaryotic Pus1 biology. Here, we show that Schizosaccharomyces pombe pus1Δ mutants are temperature sensitive due to decay of tRNAIle(UAU), as tRNAIle(UAU) levels are reduced, and its overexpression suppresses the defect.
View Article and Find Full Text PDFA non-canonical role for the tyrosyl tRNA synthetase: YARS regulates senescence induction and escape and controls the transcription of LIN9.
FEBS J
January 2025
Université d'Angers, Inserm, CNRS, CRCI2NA, ICO, Angers, France.
Senescence is a tumor suppressor mechanism triggered by oncogene expression and chemotherapy treatment. It orchestrates a definitive cessation of cell proliferation through the activation of the p53-p21 and p16-Rb pathways, coupled with the compaction of proliferative genes within heterochromatin regions. Some cancer cells have the ability to elude this proliferative arrest but the signaling pathways involved in circumventing senescence remain to be characterized.
View Article and Find Full Text PDFOptimization of ACE-tRNAs function in translation for suppression of nonsense mutations.
Nucleic Acids Res
December 2024
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY 14642, USA.
Nonsense suppressor transfer RNAs (tRNAs) or AntiCodon-Edited tRNAs (ACE-tRNAs) have long been envisioned as a therapeutic approach to overcome genetic diseases resulting from the introduction of premature termination codons (PTCs). The ACE-tRNA approach for the rescue of PTCs has been hampered by ineffective delivery through available modalities for gene therapy. Here we have screened a series of ACE-tRNA expression cassette sequence libraries containing >1800 members in an effort to optimize ACE-tRNA function and provide a roadmap for optimization in the future.
View Article and Find Full Text PDFSuppression of amber stop codons impairs pathogenicity in Salmonella.
FEBS Lett
December 2024
Department of Cell Biology and Molecular Genetics, The University of Maryland, College Park, MD, USA.
Translation terminates at UAG (amber), UGA (opal), and UAA (ochre) stop codons. In nature, readthrough of stop codons can be substantially enhanced by suppressor tRNAs. Stop-codon suppression also provides powerful tools in synthetic biology and disease treatment.
View Article and Find Full Text PDFAND Logic Based on Suppressor tRNAs Enables Stringent Control of Sliding Base Editors in .
ACS Synth Biol
December 2024
Systems Biology Department, Centro Nacional de Biotecnología-CSIC, Campus de Cantoblanco, Madrid 28049, Spain.
Base editors, e.g., cytosine deaminases, are powerful tools for precise DNA editing , enabling both targeted nucleotide conversions and segment-specific diversification of bacterial genomes.
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