Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery.
Influenza A virus NS1 protein (NS1A protein) via its effector domain targets the poly(A)-binding protein II (PABII) of the cellular 3'-end processing machinery. In vitro the NS1A protein binds the PABII protein, and in vivo causes PABII protein molecules to relocalize from nuclear speckles to a uniform distribution throughout the nucleoplasm. In vitro the NS1A protein inhibits the ability of PABII to stimulate the processive synthesis of long poly(A) tails catalyzed by poly(A) polymerase (PAP). Such inhibition also occurs in vivo in influenza virus-infected cells, where the NS1A protein via its effector domain causes the nuclear accumulation of cellular pre-mRNAs which contain short ( approximately 12 nucleotide) poly(A) tails. Consequently, although the NS1A protein also binds the 30 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF), 3' cleavage of some cellular pre-mRNAs still occurs in virus-infected cells, followed by the PAP-catalyzed addition of short poly(A) tails. Subsequent elongation of these short poly(A) tails is blocked because the NS1A protein inhibits PABII function. Nuclear-cytoplasmic shuttling of PABII, an activity implicating this protein in the nuclear export of cellular mRNAs, is also inhibited by the NS1A protein. In vitro assays suggest that the 30 kDa CPSF and PABII proteins bind to non-overlapping regions of the NS1A protein effector domain and indicate that these two 3' processing proteins also directly bind to each other.
Chen
Z
Z
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855, USA.
Li
Y
Y
Krug
R M
RM
D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D019084:Fluorescent Antibody Technique, Indirect; D009980:Influenza A virus / Q000378:metabolism; D018613:Microscopy, Confocal; D039102:Poly(A)-Binding Proteins; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
D017931:DNA Primers; C085820:INS1 protein, influenza virus; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins