RT Journal Article
SR Electronic
T1 The translational landscape of SARS-CoV-2 and infected cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.03.367516
DO 10.1101/2020.11.03.367516
A1 Maritza Puray-Chavez
A1 Kasyap Tenneti
A1 Hung R. Vuong
A1 Nakyung Lee
A1 Yating Liu
A1 Amjad Horani
A1 Tao Huang
A1 James Brett Case
A1 Wei Yang
A1 Michael S. Diamond
A1 Steven L. Brody
A1 Joseph Dougherty
A1 Sebla B. Kutluay
YR 2020
UL http://biorxiv.org/content/early/2020/11/05/2020.11.03.367516.abstract
AB SARS-CoV-2, a betacoronavirus with a positive-sense RNA genome, has caused the ongoing COVID-19 pandemic. Although a large number of transcriptional profiling studies have been conducted in SARS-CoV-2 infected cells, little is known regarding the translational landscape of host and viral proteins. Here, using ribosome profiling in SARS-CoV-2-infected cells, we identify structural elements that regulate viral gene expression, alternative translation initiation events, as well as host responses regulated by mRNA translation. We found that the ribosome density was low within the SARS-CoV-2 frameshifting element but high immediately downstream, which suggests the utilization of a highly efficient ribosomal frameshifting strategy. In SARS-CoV-2-infected cells, although many chemokine, cytokine and interferon stimulated genes were upregulated at the mRNA level, they were not translated efficiently, suggesting a translational block that disarms host innate host responses. Together, these data reveal the key role of mRNA translation in SARS-CoV-2 replication and highlight unique mechanisms for therapeutic development.HighlightsRibo-seq reveals key translationally regulated events in SARS-CoV-2 replicationSARS-CoV-2 frameshifting is substantially more efficient than HIV-1SARS-CoV-2 infection results in transcriptional upregulation of inflammatory and interferon-stimulated genesSARS-CoV-2 disarms host responses at the level of mRNA translationCompeting Interest StatementThe authors have declared no competing interest.