Since its emergence, SARS-CoV-2 has been continuously evolving. Adaptations involve nucleotide changes in the viral genome, in both coding and non-coding regions. For example, mutations in the spike gene can result in new variants with enhanced transmission and immune evasion. In coronaviruses, structural and accessory proteins are translated from subgenomic RNAs (sgmRNAs), the synthesis of which is controlled by transcription regulatory sequences (TRSs) in the 5′ genomic leader (TRS-L) and upstream of each body open reading frame (ORF) (TRS-B). In SARS-CoV-2, the TRS has a consensus sequence that evolves frequently, leading to novel sgmRNAs associated with emerging variants. A recent study by Mears et al. investigated a new sgmRNA and its role during infection.
The authors analysed SARS-CoV-2 genome sequences and identified novel TRS-B sites across the genome throughout SARS-CoV-2 evolution. The most common novel TRS-B is located within the nucleocapsid (N) coding region, leading to a new sgmRNA, N.iORF3. Mutagenesis and protein assays revealed that N.iORF3 sgmRNA encodes a truncated C-terminal portion of nucleocapsid, which inhibits type I interferon induction via RIG-I antagonism and increases viral fitness in vitro.
This is a preview of subscription content, access via your institution
Access options
/* style specs start */ /* style specs