Figure 4
Biogenesis models of sfRNA flaviruses and ncRNA3 BNYVV. A) Top, schematic representation of West Nile virus (WNV) genome. XRN1 spreading on RNA is inhibited (full red stars) by the formation of pseudoknots (shown in blue) at SL-II and SL-IV positions leading to subsequent sfRNA1 and sfRNA2 accumulation. Almost all flaviviruses ensure sfRNA1 and sfRNA2 expression and additional species, sfRNA3 and sfRNA4 (empty red stars), may accumulate depending on flaviviruses and host studied (human, mosquito, cell cultures). SfRNAs seem to be a decoy for Dicer and Ago2 and viral siRNAs (vsiRNAs) accumulate. SL-II and SL-IV structures are also described as xrRNA1 and xrRNA2 (Xrn1-resistant RNA). SL, stem-loop; DB, dumbbell; ORF, open reading frame; UTR, untranslated region. The black sphere corresponds to the cap. For review see [211]. Image adapted from [212]. B) A population of BNYVV genomic RNA3 is degraded from 5‘ to 3’ by XRN4 exoribonuclease activity. About 1230 nucleotides are thus eliminated, including the open reading frame (ORF). The progression of XRN4 is blocked by the coremin sequence and non-coding RNA3 (ncRNA3) accumulate. A structural element containing the coremin sequence seems to induce XRN4 stalling, but this structure remains to be determined. A comparable degradation mechanism is described for BNYVV RNA5 [169].