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Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome.
Bhatt, Pramod R; Scaiola, Alain; Loughran, Gary; Leibundgut, Marc; Kratzel, Annika; Meurs, Romane; Dreos, René; O'Connor, Kate M; McMillan, Angus; Bode, Jeffrey W; Thiel, Volker; Gatfield, David; Atkins, John F; Ban, Nenad.
  • Bhatt PR; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Scaiola A; School of Biochemistry and Cell Biology, University College Cork, Cork T12 XF62, Ireland.
  • Loughran G; School of Microbiology, University College Cork, Cork T12 K8AF, Ireland.
  • Leibundgut M; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Kratzel A; School of Biochemistry and Cell Biology, University College Cork, Cork T12 XF62, Ireland.
  • Meurs R; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Dreos R; Institute of Virology and Immunology, University of Bern, Bern, Switzerland.
  • O'Connor KM; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • McMillan A; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
  • Bode JW; Center for Integrative Genomics, Génopode, University of Lausanne, 1015 Lausanne, Switzerland.
  • Thiel V; Center for Integrative Genomics, Génopode, University of Lausanne, 1015 Lausanne, Switzerland.
  • Gatfield D; School of Biochemistry and Cell Biology, University College Cork, Cork T12 XF62, Ireland.
  • Atkins JF; Laboratorium für Organische Chemie, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
  • Ban N; Laboratorium für Organische Chemie, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
Science ; 372(6548): 1306-1313, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1228853
Preprint
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Semantic information from SemMedBD (by NLM)
1. Ribosomes PART_OF Mammals
Subject
Ribosomes
Predicate
PART_OF
Object
Mammals
2. RN CAUSES C0233494
Subject
RN
Predicate
CAUSES
Object
C0233494
3. Ribosomes PART_OF Mammals
Subject
Ribosomes
Predicate
PART_OF
Object
Mammals
4. RNA, Viral CAUSES Tension
Subject
RNA, Viral
Predicate
CAUSES
Object
Tension
ABSTRACT
Programmed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis of the viral RNA-dependent RNA polymerase and downstream proteins. Here, we present the cryo-electron microscopy structure of a translating mammalian ribosome primed for frameshifting on the viral RNA. The viral RNA adopts a pseudoknot structure that lodges at the entry to the ribosomal messenger RNA (mRNA) channel to generate tension in the mRNA and promote frameshifting, whereas the nascent viral polyprotein forms distinct interactions with the ribosomal tunnel. Biochemical experiments validate the structural observations and reveal mechanistic and regulatory features that influence frameshifting efficiency. Finally, we compare compounds previously shown to reduce frameshifting with respect to their ability to inhibit SARS-CoV-2 replication, establishing coronavirus frameshifting as a target for antiviral intervention.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Ribosomes / Viral Proteins / RNA, Viral / Frameshifting, Ribosomal / SARS-CoV-2 Type of study: Observational study / Prognostic study Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: Science.abf3546

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ribosomes / Viral Proteins / RNA, Viral / Frameshifting, Ribosomal / SARS-CoV-2 Type of study: Observational study / Prognostic study Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: Science.abf3546