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| 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
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| 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.
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| Overall design |
Ribosome profiling of SARS-CoV-2 in-vitro translation
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| Web link |
https://science.sciencemag.org/content/early/2021/05/12/science.abf3546
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| 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 |
| E-mail(s) |
rene.dreos@unil.ch
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| Phone |
0044 (0)1603 450793
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| Organization name |
UNIL
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| Department |
CIG
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| Lab |
Gatfield Lab
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| Street address |
Ecublens
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| City |
Lausanne |
| State/province |
VD |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL29767 |
Illumina HiSeq 2500 (Severe acute respiratory syndrome coronavirus 2) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA704627 |
| SRA |
SRP307946 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE167421_RAW.tar |
20.0 Kb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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