PMID- 24891509 OWN - NLM STAT- MEDLINE DCOM- 20141006 LR - 20220129 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 29 DP - 2014 Jul 18 TI - The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export. PG - 20067-77 LID - 10.1074/jbc.M114.569178 [doi] AB - In influenza A virus-infected cells, replication and transcription of the viral genome occurs in the nucleus. To be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein (NEP) is involved in both processes. Although NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with viral ribonucleoprotein (vRNP)-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are linked functionally. Here we provide evidence that the interaction between M1 and the vRNP depends on the NEP C terminus and its polymerase activity-enhancing property for the nuclear export of vRNPs. This suggests that these features of NEP are linked functionally. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C terminus. On the basis of our data, we propose a new model for the assembly of the nuclear export complex of Influenza A vRNPs. CI - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Brunotte, Linda AU - Brunotte L AD - From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and. FAU - Flies, Joe AU - Flies J AD - From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and. FAU - Bolte, Hardin AU - Bolte H AD - From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and. FAU - Reuther, Peter AU - Reuther P AD - From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and. FAU - Vreede, Frank AU - Vreede F AD - the Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford OX 3RE, United Kingdom. FAU - Schwemmle, Martin AU - Schwemmle M AD - From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and martin.schwemmle@uniklinik-freiburg.de. LA - eng GR - G1100138/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140602 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (M1 protein, Influenza A virus) RN - 0 (Nucleocytoplasmic Transport Proteins) RN - 0 (RNA, Viral) RN - 0 (Recombinant Proteins) RN - 0 (Ribonucleoproteins) RN - 0 (Viral Matrix Proteins) RN - 0 (Viral Proteins) SB - IM MH - Active Transport, Cell Nucleus MH - HEK293 Cells MH - Humans MH - Influenza A Virus, H5N1 Subtype/genetics/*metabolism MH - Models, Biological MH - Nucleocytoplasmic Transport Proteins/chemistry/genetics/*metabolism MH - Protein Interaction Domains and Motifs MH - RNA, Viral/biosynthesis/genetics MH - Recombinant Proteins/chemistry/genetics/metabolism MH - Ribonucleoproteins/chemistry/genetics/*metabolism MH - Sequence Deletion MH - Transcription, Genetic MH - Viral Matrix Proteins/chemistry/genetics/*metabolism MH - Viral Proteins/chemistry/genetics/*metabolism MH - Virus Replication PMC - PMC4106323 OTO - NOTNLM OT - Influenza Virus OT - Protein Export OT - Ribonucleoprotein (RNP) OT - Viral Polymerase OT - Viral Protein EDAT- 2014/06/04 06:00 MHDA- 2014/10/07 06:00 PMCR- 2015/07/18 CRDT- 2014/06/04 06:00 PHST- 2014/06/04 06:00 [entrez] PHST- 2014/06/04 06:00 [pubmed] PHST- 2014/10/07 06:00 [medline] PHST- 2015/07/18 00:00 [pmc-release] AID - S0021-9258(20)47656-2 [pii] AID - M114.569178 [pii] AID - 10.1074/jbc.M114.569178 [doi] PST - ppublish SO - J Biol Chem. 2014 Jul 18;289(29):20067-77. doi: 10.1074/jbc.M114.569178. Epub 2014 Jun 2.