Host mRNAs poly(A) tail is added in two steps. First, pre-mRNAs are cleaved and a short poly(A) tail is added. Subsequent elongation of this short poly(A) tail requires poly(A)-binding protein II, CPSF complex and PAP (PABII), which facilitate rapid, processive poly(A) addition. PABII also plays a role in nuclear export of host mRNAs.
Some viruses interfere with host pre-mRNA processing function. Incompletely processed mRNA are non-functional leading to shutoff of host proteins expression. This gives viruses transcripts a competitive edge for access to the cellular translation machinery. Preventing the expression of host proteins is also a strategy to counteract the antiviral response.
Some viruses have been shown to inhibit host pre-mRNA processing by blocking cellular splicing or polyadenylation.
Herpesvirus protein ICP27 mediates the inhibition of cellular splicing. Early in infection, ICP27 interacts with several splicing factors, including members of a family of essential splicing factors termed SR proteins, and affects their phosphorylation. This results in the blockage of the pre-spliceosome assembly, which in turn contributes to the shutoff of host protein synthesis because of incomplete cellular pre-mRNAs processing.
Influenza virus NS1 can bind to CPSF30 and PABII and thus inhibits host pre-mRNA processing.
NS1 of the 2009 Pandemic H1N1 has a truncated C-terminus and has apparently lost the ability to bind PABII
Viruses inhibiting host mRNA splicing:
|Family||Virus||Viral protein||mRNA processing inhibition strategy||references|
|Orthomyxoviridae||Influenza A virus||NS1||Inhibition of polyadenylation via binding to CPSF30 and PABII|
|Herpesviridae||HHV1, HHV2||ICP27||Inhibition of splicing|
|Retroviridae||HIV-1||VPR||Inhibition of splicing|