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Series GSE167421 Query DataSets for GSE167421
Status Public on May 17, 2021
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Organism Severe acute respiratory syndrome coronavirus 2
Experiment type Other
Summary Programmed ribosomal frameshifting is the key event during translation of the SARS-CoV-2 RNA genome allowing synthesis of the viral RNA-dependent RNA polymerase and downstream viral proteins. Here we present the cryo-EM structure of the mammalian ribosome in the process of translating viral RNA paused in a conformation primed for frameshifting. We observe that the viral RNA adopts a pseudoknot structure lodged at the mRNA entry channel of the ribosome to generate tension in the mRNA that leads to frameshifting. The nascent viral polyprotein that is being synthesized by the ribosome paused at the frameshifting site forms distinct interactions with the ribosomal polypeptide exit tunnel. We use biochemical experiments to validate our structural observations and to reveal mechanistic and regulatory features that influence the frameshifting efficiency. Finally, a compound previously shown to reduce frameshifting is able to inhibit SARS-CoV-2 replication in infected cells, establishing coronavirus frameshifting as target for antiviral intervention.
Overall design Ribosome profiling of SARS-CoV-2 in-vitro translation
Web link
Contributor(s) Bhatt PR, Scaiola A, Loughran G, Leibundgut M, Kratzel A, McMillan A, O’ Connor KM, Bode JW, Thiel V, Atkins JF, Meurs R, Dreos R, Gatfield D, Ban N
Citation(s) 34029205
Submission date Feb 24, 2021
Last update date Aug 16, 2021
Contact name Rene Dreos
Phone 0044 (0)1603 450793
Organization name UNIL
Department CIG
Lab Gatfield Lab
Street address Ecublens
City Lausanne
State/province VD
ZIP/Postal code 1015
Country Switzerland
Platforms (1)
GPL29767 Illumina HiSeq 2500 (Severe acute respiratory syndrome coronavirus 2)
Samples (4)
GSM5105026 Monosome – Wild Type
GSM5105027 Disomes – Wild type
GSM5105028 Monosome – Mutant
BioProject PRJNA704627
SRA SRP307946

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Supplementary file Size Download File type/resource
GSE167421_RAW.tar 20.0 Kb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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