2023-09-12 18:34:15
In an article published in the journal Nucleic Acids Research, Scientists have studied how the SARS-CoV-2 virus promotes the translation of its own genome in infected cells by disabling cellular translation. During the early stages of infection, the NSP1 protein is one of the first viral proteins produced. This NSP1 protein will immediately attach to the ribosome of the host cell. The researchers showed that the NSP1 protein on the ribosome will induce regularly spaced cuts in the cell’s messenger RNAs as the ribosome advances on these messenger RNAs. Thus, all messenger RNAs that are translated will be degraded due to the presence of the NSP1 protein. However, the translation of mRNAs is a fundamental process which allows the cell to produce the proteins necessary for its survival, its functioning and its responses to external stimuli.
The RNA of the SARS-CoV-2 virus escapes this degradation
Among the messenger RNAs targeted as a priority, messenger RNAs coding for proteins necessary for the antiviral response, such as interferons, will be degraded as a priority. Thus, thanks to this molecular mechanism, the virus blocks the cell’s antiviral reactions. On the other hand, the RNA of the SARS-CoV-2 virus escapes this degradation and is translated normally. Scientists have shown that the virus’s RNA is immune to this degradation guided by the NSP1 protein. Indeed, the virus has in its messenger RNAs a small hairpin structure called SL1 which allows it to protect its RNAs against degradation on the ribosome by acting on NSP1. The virus somehow has a key that allows it to continue viral translation while cellular translation gradually turns off.
The ‘Achilles heel’ of the SARS-CoV-2 virus
This discovery is extremely important since it opens the way to new antiviral therapeutic approaches aimed at blocking the cell cycle of the virus. Indeed, the essential role of SL1 in the infectious process makes this element of the virus a prime target for the development of new inhibitor molecules. Such molecules would be capable of specifically blocking the action of SL1, thus making it possible to turn off the translation of the virus. In summary, the fact that SL1 is essential for viral translation suggests that this structure would be a real ‘Achilles heel’ of the virus.
The NSP1 protein of the SARS-CoV-2 virus binds to the small 40S subunit of the cell’s ribosome during the early phases of infection and induces cuts in messenger RNAs during their translation. This makes it possible to quickly turn off cellular translation and disrupt the cell’s antiviral defense mechanisms. © Franck MARTIN
SARS-CoV-2 NSP1 induces mRNA cleavages on the ribosome; Yann TARDIVAT, Piotr SOSNOWSKI, Antonin TIDU, Eric WESTHOF, Gilbert ERIANI, Franck MARTIN*. Published in Nucleic Acids Research; DOI: 10.1093/nar/gkad627
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