Insight into Influenza: A Virus Cap-Snatching

Abstract

The influenza A virus (IAV) genome consists of eight single-stranded RNA segments. Each segment is associated with a protein complex, with the 3' and 5' ends bound to the RNA-dependent RNA polymerase (RdRp) and the remainder associated with the viral nucleoprotein. During transcription of viral mRNA, this ribonucleoprotein complex steals short, 5'-capped transcripts produced by the cellular DNA dependent RNA polymerase II (RNAPII) and uses them to prime transcription of viral mRNA. Here, we review the current knowledge on the process of IAV cap-snatching and suggest a requirement for RNAPII promoter-proximal pausing for efficient IAV mRNA transcription.

Keywords: cap-snatching; influenza A virus; prime-and-realign; promoter-proximal pausing.

Figure 1

Cartoon representation of influenza A virus (IAV) RNA-dependent RNA polymerase (RdRp) bound to the viral RNA (vRNA) promoter and priming transcription. The PB1 subunit (blue) has two entrance tunnels, one occupied by the vRNA coming from the nucleoprotein (yellow), the other allowing nucleoside triphosphates (NTPs) to enter the active site. The two entrance tunnels join at the active site and split into the template exit tunnel (left, where the vRNA exits near PA opposite to the endonuclease) and the product exit tunnel. Cap snatched primers are threaded through the product exit tunnel to prime transcription. The distance from the PB2 cap binding region to the PB1 active site has been estimated to be 54 angstroms. The distance from the PB2 cap binding region to the endonuclease active site has been estimated to be 50 angstroms [11]. The 5′ end of the vRNA is tightly held in a binding pocket, and there are five base pairs between the 3′ end and the 5′ end of the vRNA. The nucleotides 3′-UCGUUUU are not bound to the polymerase. An A indicates an adenine residue, C indicates a cytidine residue, G indicates a guanine residue, U indicates a uridine residue, and N indicates a nucleotide residue. Nucleotides labeled as N within the vRNA are gene segment specific. Hashed lines indicate putative base pairs between the vRNA promoter and the host primer.