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Role of ran binding protein 5 in nuclear import and assembly of the influenza virus RNA polymerase complex.
- Source :
-
Journal of virology [J Virol] 2006 Dec; Vol. 80 (24), pp. 11911-9. Date of Electronic Publication: 2006 Sep 27. - Publication Year :
- 2006
-
Abstract
- The influenza A virus RNA-dependent RNA polymerase is a heterotrimeric complex of polymerase basic protein 1 (PB1), PB2, and polymerase acidic protein (PA) subunits. It performs transcription and replication of the viral RNA genome in the nucleus of infected cells. We have identified a nuclear import factor, Ran binding protein 5 (RanBP5), also known as karyopherin beta3, importin beta3, or importin 5, as an interactor of the PB1 subunit. RanBP5 interacted with either PB1 alone or with a PB1-PA dimer but not with a PB1-PB2 dimer or the trimeric complex. The interaction between RanBP5 and PB1-PA was disrupted by RanGTP in vitro, allowing PB2 to bind to the PB1-PA dimer to form a functional trimeric RNA polymerase complex. We propose a model in which RanBP5 acts as an import factor for the newly synthesized polymerase by targeting the PB1-PA dimer to the nucleus. In agreement with this model, small interfering RNA (siRNA)-mediated knock-down of RanBP5 inhibited the nuclear accumulation of the PB1-PA dimer. Moreover, siRNA knock-down of RanBP5 resulted in the delayed accumulation of viral RNAs in infected cells, confirming that RanBP5 plays a biological role during the influenza virus life cycle.
- Subjects :
- Active Transport, Cell Nucleus physiology
Amino Acid Sequence
Base Sequence
Cell Line
DNA Primers
Dimerization
Electrophoresis, Polyacrylamide Gel
Humans
Models, Biological
Molecular Sequence Data
Protein Binding
RNA Interference
Sequence Analysis, DNA
Cell Nucleus metabolism
DNA-Directed RNA Polymerases biosynthesis
Influenza A virus metabolism
Viral Proteins biosynthesis
beta Karyopherins genetics
beta Karyopherins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 80
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 17005651
- Full Text :
- https://doi.org/10.1128/JVI.01565-06