Secondary structure of the SARS-CoV-2 5'-UTR

The SARS-CoV-2, a positive-sense single-stranded RNA Coronavirus, is a global threat to human health. Thus, understanding its life cycle mechanistically would be important to facilitate the design of antiviral drugs. A key aspect of viral progression is the synthesis of viral proteins by the ribosome of the human host. In Coronaviruses, this process is regulated by the viral 5MODIFIER LETTER PRIME and 3MODIFIER LETTER PRIME untranslated regions (UTRs), but the precise regulatory mechanism has not yet been well understood. In particular, the 5MODIFIER LETTER PRIME-UTR of the viral genome is most likely involved in translation initiation of viral proteins. Here, we performed inline probing and RNase V1 probing to establish a model of the secondary structure of SARS-CoV-2 5MODIFIER LETTER PRIME-UTR. We found that the 5MODIFIER LETTER PRIME-UTR contains stable structures including a very stable four-way junction close to the AUG start codon. Sequence alignment analysis of SARS-CoV-2 variants 5MODIFIER LETTER PRIME-UTRs revealed a highly conserved structure with few co-variations that confirmed our secondary structure model based on probing experiments.

Automated summary

The 5'UTR of SARS-CoV-2 contains stable structures, including a very stable four-way junction close to the AUG start codon. Sequence alignment analysis of SARS-CoV-2 variants' 5'UTRs revealed a highly conserved structure with few co-variations, confirming the secondary structure model based on probing experiments.