title: New nsp8 isoform suggests mechanism for tuning viral RNA synthesis.
abstract: During severe acute respiratory syndrome coronavirus (SARS-CoV) infection, the activity of the replication/transcription complexes (RTC) quickly peaks at 6 hours post infection (h.p.i) and then diminishes significantly in the late post-infection stages. This "down-up-down" regulation of RNA synthesis distinguishes different viral stages: primary translation, genome replication, and finally viron assembly. Regarding the nsp8 as the primase in RNA synthesis, we confirmed that the proteolysis product of the primase (nsp8) contains the globular domain (nsp8C), and indentified the resectioning site that is notably conserved in all the three groups of coronavirus. We subsequently crystallized the complex of SARS-CoV nsp8C and nsp7, and the 3-D structure of this domain revealed its capability to interfuse into the hexadecamer super-complex. This specific proteolysis may indicate one possible mechanism by which coronaviruses to switch from viral infection to genome replication and viral assembly stages.
authors.affiliation: National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Yinjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Bartlam
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019915:DNA Primase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000096:biosynthesis*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D045169:Severe Acute Respiratory Syndrome / Q000821:virology*; D014779:Virus Replication
chemical_list: D007527:Isoenzymes; D012367:RNA, Viral; D019915:DNA Primase