Meta-Biol

• Pathways

SARS-CoV-1 encodes eight subgenomic RNAs, mRNA2 to mRNA9. mRNA1 corresponds to the genomic RNA. The 5' and 3' ends of subgenomic RNAs are identical, in accordance with the template switch model of coronavirus RNA transcription (Snijder et al. 2003, Thiel et al. 2003, Yount et al. 2003). Therefore, consistent with this and the studies of the murine hepatitis virus (MHV), which is closely related to SARS-CoV-1, genomic positive strand RNA is first transcribed into negative sense (minus strand) subgenomic mRNAs, that subsequently serve as templates for the synthesis of positive strand subgenomic mRNAs. Negative-sense virus RNAs are present in much smaller amounts than positive-sense RNAs (Irigoyen et al. 2016). Each subgenomic RNA contains a leader transcription regulatory sequence (leader TRS) that is identical to the leader of the genome, appended via polymerase “jumping” during negative strand synthesis to the body transcription regulatory sequence (body TRS), a short, AU-rich motif of about 10 nucleotides found upstream of each ORF that is destined to become 5' proximal in one of the subgenome-length mRNAs. The 3' and 5'UTRs may interact through RNA–RNA and/or RNA–protein plus protein–protein interactions to promote circularization of the coronavirus genome, placing the elongating minus strand in a favorable topology for leader-body joining. The host protein PABP was found to bind to the coronavirus 3' poly(A) tail and to interact with the host protein eIF-4G, a component of the three-subunit complex that binds to mRNA cap structures, which may promote the circularization of the coronavirus genome. Two viral proteins that bind to the coronavirus 5'UTR, the N protein and nsp1, may play a role in template switching. The poly(A) tail is necessary for the initiation of minus-strand RNA synthesis at the 3' end of genomic RNA. For review, please refer to Sawicki et al. 2007 and Yang and Leibowitz 2015.