Société Française de Biochimie et Biologie Moléculaire


Institut de Biologie Moléculaire et Cellulaire - UPR-9002 (CNRS) 
"The viral protein NSP1 acts as a ribosome gatekeeper for shutting down host translation and fostering SARS-CoV-2 translation." RNA 27, 253–264 (2021) PMID: 33268501 PMCID: PMC7901841 DOI: 10.1261/rna.078121.120
Antonin Tidu, Aurélie Janvier, Laure Schaeffer, Piotr Sosnowski, Lauriane Kuhn, Philippe Hamman, Eric Westhof, Gilbert Eriani and Franck Martin.


Antonin Tidu, 25 year old, obtained in 2018 an engineering degree from “Ecole Supérieure de Biotechnologies de Strasbourg” and is currently a PhD student in the team "Evolution of translation initiation systems in eukaryotes" within the CNRS UPR 9002 - RNA, under the supervision of Franck Martin. His work is focusing on the molecular mechanisms of translation initiation regulation in eukaryotes and more precisely, the characterization of IRES (Internal Ribosome Entry Site) in viral genomes. In the selected publication in RNA, Antonin Tidu and collaborators describe how the viral protein NS1 from SARS-CoV-2, one of the first viral proteins that is produced at the onset of the infectious program, hijacks the host translation machinery. NSP1 binding to the ribosome prevents entry of mRNA in the mRNA channel. Thanks to the specific stem-loop structure SL1 present in the 5 ′ UTR of all viral RNAs, viral translation is evading NSP1-mediated inhibition. By interacting with the 40S-NSP1 complex, this structure enables viral mRNA accommodation and the formation of translation initiation complexes. This study reveals that NSP1 acts as a ribosome gatekeeper to promote viral translation making this stem-loop SL1 an attractive target for development of novel therapeutic strategies in the fight against the new SARS-CoV-2.


Institut de Biologie Moléculaire et Cellulaire - UPR-9002 (CNRS) 

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Summury of the article

During the early stages of infection, the NSP1 protein is one of the first viral proteins produced. This NSP1 protein will immediately bind to the ribosome of the host cell and block the entry site to prevent access of the cell's messenger RNAs, which will then no longer be translated. In this way, the virus takes control of the cell's translational machinery and literally turns off cellular translation. However, the virus genome continues to be translated despite the presence of NSP1 on the ribosome. The experiments carried out made it possible to understand how the virus can bypass this blockage by the NSP1 protein. The virus has a small hairpin structure called SL1 in its messenger RNAs that allows it to open up access to the ribosome by acting on NSP1. The virus has a sort of key that allows it to continue translating by unlocking the ribosome blocked by the viral protein NSP1 during infection. This discovery is extremely important as it opens the way to new antiviral therapeutic approaches aimed at blocking the virus' cell cycle. Indeed, the primordial role of SL1 in the infection process makes this element of the virus a prime target for the development of new inhibiting molecules. Such molecules would be capable of specifically blocking the action of SL1, thus enabling the virus to be turned off. In short, the fact that SL1 is essential for viral translation suggests that this structure is a real 'Achilles heel' of the virus.