Cellular RNA Binding Proteins NS1-BP and hnRNP K Regulate Influenza A Virus RNA Splicing

• DOI: 10.1371/journal.ppat.1003460
• Publication Date: 2013-06-27T21:05:49Z
• Authors: Pei-Ling Tsai; Ni-Ting Chiou; Sharon Kuss; Adolfo García-Sastre; Kristen W. Lynch; Beatriz M. A. Fon...
• Keywords: Heterogeneous ribonucleoprotein particle; SR protein; Heterogeneous nuclear ribonucleoprotein; Exonic splicing enhancer

Influenza A virus is a major human pathogen with genome comprised of eight single-strand, negative-sense, RNA segments. Two viral segments, NS1 and M, undergo alternative splicing yield several proteins including NS1, NS2, M1 M2 proteins. However, the mechanisms or players involved in these segments have not been fully studied. Here, by investigating interacting partners function cellular protein NS1-binding (NS1-BP), we revealed novel segment. Using proteomics approach, identified complex binding containing NS1-BP heterogeneous nuclear ribonucleoproteins (hnRNPs), among which are hnRNPs host pre-mRNA splicing. We found that low levels specifically impaired proper mRNA segment to without affecting mRNA3, M4, NS Further biochemical analysis formaldehyde UV cross-linking demonstrated did interact directly but its partners, A1, K, L, bound mRNA. Among hnRNPs, hnRNP K as mediator The generates matrix ion channel, essential trafficking, release into cytoplasm, budding. Thus, reduction and/or altered M2/M1 ratios, decreasing inhibiting replication. NS1-BP-hnRNPK key influenza gene expression.