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Emergence of new subgenomic mRNAs in SARS-CoV-2
Harriet V Mears; George R Young; Theo Sanderson; Ruth Harvey; Margaret Crawford; Daniel M Snell; Ashley S Fowler; Saira Hussain; Jerome Nicod; Edward Emmott; Katja Finsterbusch; Jakub Luptak; Emma Wall; Bryan Williams; Sonia Gandhi; Charles Swanton; David LV Bauer.
Afiliación
  • Harriet V Mears; RNA Virus Replication Laboratory, The Francis Crick Institute, London, UK
  • George R Young; RNA Virus Replication Laboratory & Bioinformatics and Biostatistics STP, The Francis Crick Institute, London, UK
  • Theo Sanderson; Malaria Biochemistry Laboratory, The Francis Crick Institute, London, UK
  • Ruth Harvey; Worldwide Influenza Centre, The Francis Crick Institute, London, UK
  • Margaret Crawford; Advanced Sequencing Facility, The Francis Crick Institute, London, UK
  • Daniel M Snell; Advanced Sequencing Facility, The Francis Crick Institute, London, UK
  • Ashley S Fowler; Advanced Sequencing Facility, The Francis Crick Institute, London, UK
  • Saira Hussain; RNA Virus Replication Laboratory, The Francis Crick Institute, London, UK
  • Jerome Nicod; Advanced Sequencing Facility, The Francis Crick Institute, London, UK
  • Edward Emmott; Centre for Proteome Research, Department of Biochemistry & Systems Biology, Institute of Systems Molecular & Integrative Biology, University of Liverpool, Liver
  • Katja Finsterbusch; Immunoregulation Laboratory, The Francis Crick Institute, London, UK
  • Jakub Luptak; MRC Laboratory of Molecular Biology, Cambridge, UK
  • Emma Wall; Crick/UCLH Legacy Study, The Francis Crick Institute, London, UK; and National Institute for Health Research (NIHR) University College London Hospitals (UCLH) B
  • Bryan Williams; University College London; and National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, UK
  • Sonia Gandhi; Neurodegeneration Biology Laboratory, The Francis Crick Institute, London, UK
  • Charles Swanton; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK
  • David LV Bauer; RNA Virus Replication Laboratory, The Francis Crick Institute, London, UK
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-488895
ABSTRACT
Two mutations occurred in SARS-CoV-2 early during the COVID-19 pandemic that have come to define circulating virus lineages1 first a change in the spike protein (D614G) that defines the B.1 lineage and second, a double substitution in the nucleocapsid protein (R203K, G204R) that defines the B.1.1 lineage, which has subsequently given rise to three Variants of Concern Alpha, Gamma and Omicron. While the latter mutations appear unremarkable at the protein level, there are dramatic implications at the nucleotide level the GGG[->]AAC substitution generates a new Transcription Regulatory Sequence (TRS) motif, driving SARS-CoV-2 to express a novel subgenomic mRNA (sgmRNA) encoding a truncated C-terminal portion of nucleocapsid (N.iORF3), which is an inhibitor of type I interferon production. We find that N.iORF3 also emerged independently within the Iota variant, and further show that additional TRS motifs have convergently evolved to express novel sgmRNAs; notably upstream of Spike within the nsp16 coding region of ORF1b, which is expressed during human infection. Our findings demonstrate that SARS-CoV-2 is undergoing evolutionary changes at the functional RNA level in addition to the amino acid level, reminiscent of eukaryotic evolution. Greater attention to this aspect in the assessment of emerging strains of SARS-CoV-2 is warranted.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2022 Tipo del documento: Preprint