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Quantitative global studies reveal differential translational control by start codon context across the fungal kingdom

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اقرأ أكثر
  • معلومة اضافية
    • Contributors:
      Centre for Synthetic and Systems Biology (Ssynthsys); University of Edinburgh; Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS); Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens; Institut Pasteur [Paris] (IP); Department of Biochemistry and Biophysics [San Francisco]; University of California (UC); Génétique des Interactions macromoléculaires / Genetics of Macromolecular Interactions; Chan Zuckerberg BioHub [San Francisco, CA]; This work in the Madhani lab was supported by grants from the US National Institutes of Health [R01AI120464, R01GM71801 to H.D.M.]; H.D.M. is an Investigator of the Chan-Zuckerberg Biohub; E.W.J.W. is a Sir Henry Dale Fellow, supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society [208779/Z/17/Z]; L.T. is supported by a Wellcome-University of Edinburgh ISSF3 award; This work in the Janbon lab was supported by an Infect-ERA grant (project Cryptoview). Funding for open access charge: University of Edinburgh.; We thank members of the Wallace, Janbon, and Madhani labs for helpful discussions and comments on the manuscript. We thank Juan Mata for sharing intermediate data related to (59). We are grateful to J. Weissman (UCSF) for advice on ribosome profiling. We thank three anonymous reviewers for their helpful comments.; Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS); Institut Pasteur [Paris]; University of California; Génétique des Interactions macromoléculaires
    • الموضوع:
      2020
    • نبذة مختصرة :
      Eukaryotic protein synthesis generally initiates at a start codon defined by an AUG and its surrounding Kozak sequence context, but the quantitative importance of this context in different species is unclear. We tested this concept in two pathogenic Cryptococcus yeast species by genome-wide mapping of translation and of mRNA 5′ and 3′ ends. We observed thousands of AUG-initiated upstream open reading frames (uORFs) that are a major contributor to translation repression. uORF use depends on the Kozak sequence context of its start codon, and uORFs with strong contexts promote nonsense-mediated mRNA decay. Transcript leaders in Cryptococcus and other fungi are substantially longer and more AUG-dense than in Saccharomyces. Numerous Cryptococcus mRNAs encode predicted dual-localized proteins, including many aminoacyl-tRNA synthetases, in which a leaky AUG start codon is followed by a strong Kozak context in-frame AUG, separated by mitochondrial-targeting sequence. Analysis of other fungal species shows that such dual-localization is also predicted to be common in the ascomycete mould, Neurospora crassa. Kozak-controlled regulation is correlated with insertions in translational initiation factors in fidelity-determining regions that contact the initiator tRNA. Thus, start codon context is a signal that quantitatively programs both the expression and the structures of proteins in diverse fungi.
    • File Description:
      application/pdf
    • ISSN:
      0305-1048
      1362-4962
    • الرقم المعرف:
      10.1093/nar/gkaa060
    • الرقم المعرف:
      10.1093/nar/gkaa060⟩
    • Rights:
      OPEN
    • الرقم المعرف:
      edsair.doi.dedup.....bf61a7e41b710769c98f2c49ddc7d2bf