Question

Explain the mechanism of cap snatching as described for influenza A virus. Explain how influenza virus synthesizes a poly A tail on its mRNAs.

Answer 1

ans-Cap-snatching occurs in three general steps:

1) The viral RdRp or N protein binds to the host mRNA 5’-methylated cap-1 or cap-2 structure.

2) Viral endonuclease cleaves mRNA several nucleotides downstream of the cap.

3) Capped RNA utilized as a primer to initiate viral mRNA synthesis carried out by the RdRp.

mechhanismas for influenza viruses

influenza A. In  the viral family of influenza , the RdRp is divided into three subunits: PA, PB1 and P2.

   PB1 first binds the 5’ end of the viral RNA (vRNA), activating PB2 and causing the 3’ end of the vRNA to form a double-stranded zone with the 5’ end

The PB2 proceeds to bind cellular mRNA at the N7-methyl guanosine (m7G) capped 5’ end. The PA subunit subsequently cleaves the sequence 10-13 nucleotides from the cap structure via endonuclease activity at the N terminus.

The exact cleavage location is dependent both on the distance between the PB2 and the PA of the RdRp (around 50 angstroms or 10-13 nucleotides) and also the sequence of the mRNA

Then, the PB1 subunit, which contains the polymerase activity, initially adds on two new nucleotides. The cap snatched primer moves through the product exit tunnel in the PB1 domain to serve as the primer for transcription.

The vRNA 3’-UCGUUUU nucleotides are not bound to the polymerase but rather are free for complementary binding with the capped RNA primer to confer stability

. Transcription then begins with G or C residue on the 3’ end of the capped primer.

Finally, the PB1 subunit completes chain elongation in the canonical 5’ to 3’ direction, releasing the cap, but keeping the 5’ end bound. The viral 3’ poly-A tail is added at the end of transcription by polymerase stuttering from the steric hindrance of the vRNA loop.

The resulting viral mRNA looks is identical to host mRNA, allowing endogenous cellular machinery to carry out processing and nuclear export.

the poly(A) tail of influenza virus mRNA is synthesized by reiterative copying of a U track near the 5′ end of the virion RNA (vRNA) template by the viral RNA polymerase.