Function of two discrete regions is required for nuclear localization of polymerase basic protein 1 of A/WSN/33 influenza virus (H1 N1).
Polymerase basic protein 1 (PB1) of influenza virus (A/WSN/33), when expressed from cloned cDNA in the absence of other viral proteins, accumulates in the nucleus. We have examined the location and nature of the nuclear localization signal of PB1 by using deletion mutants and chimeric constructions with chicken muscle pyruvate kinase, a cytoplasmic protein. Our studies showed some novel features of the nuclear localization signal of PB1. The signal was present internally within residues 180 to 252 of PB1. Moreover, unlike most nuclear localization signals, it was not a single stretch of contiguous amino acids. Instead, it possessed two discontinuous regions separated by an intervening sequence which could be deleted without affecting its nuclear localization property. On the other hand, deletion of either of the two signal regions rendered the protein cytoplasmic, indicating that the function of both regions is required for nuclear localization and that one region alone is not sufficient. Both of these signal regions contained short stretches of basic residues. Possible ways by which this novel bipartite signal can function in nuclear localization are discussed.
Department of Microbiology and Immunology, Jonsson Comprehensive Cancer Center, University of California-Los Angeles School of Medicine 90024-1747.
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D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002645:Chickens; D002678:Chimera; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000096:biosynthesis / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D005814:Genes, Viral; D009980:Influenza A virus / Q000235:genetics*; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics; D011770:Pyruvate Kinase / Q000235:genetics; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*
D004279:DNA, Viral; D021382:Protein Sorting Signals; D014764:Viral Proteins; D011770:Pyruvate Kinase; D012321:DNA-Directed RNA Polymerases