title: The protein arginine methyltransferase PRMT6 inhibits HIV-1 Tat nucleolar retention.
abstract: The human immunodeficiency virus (HIV)-1 transactivator protein Tat is known to play a key role in HIV infection, integrally related to its role in the host cell nucleus/nucleolus. Here we show for the first time that Tat localisation can be modulated by specific methylation, whereby overexpression of active but not catalytically inactive PRMT6 methyltransferase specifically leads to exclusion of Tat from the nucleolus. An R52/53A mutated Tat derivative does not show this redistribution, implying that R52/53, within Tat's nuclear/nucleolar localisation signal, are the targets of PRMT6 activity. Analysis using fluorescence recovery after photobleaching indicate that Tat nucleolar accumulation is largely through binding to nucleolar components, with methylation of Tat by PRMT6 preventing this. To our knowledge, this is the first report of specific protein methylation inhibiting nucleolar retention.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; Monash Micro Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Fulcher
authors.affiliation: Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia; The University of Queensland, School of Population Health, Herston, Queensland 4072, Australia.
authors.forename: Haran
authors.initials: H
authors.lastname: Sivakumaran
authors.affiliation: Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
authors.forename: Hongping
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia; School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rawle
authors.affiliation: Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia; Griffith Medical Research College, a joint program of Griffith University and the Queensland Institute of Medical Research, Queensland, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Harrich
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; ARC Centre of Excellence for Biotechnology and Development, Australia. Electronic address: David.Jans@monash.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Jans
mesh_terms: D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002466:Cell Nucleolus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D036681:Fluorescence Recovery After Photobleaching; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D018613:Microscopy, Confocal; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D000097573:Red Fluorescent Protein
chemical_list: D001120:Arginine; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D011484:Protein-Arginine N-Methyltransferases; D054322:tat Gene Products, Human Immunodeficiency Virus; D000097573:Red Fluorescent Protein; C447833:PRMT6 protein, human
keywords: HIV-1 Rev; HIV-1 Tat; HTLV-1 Rex; Methyltransferase PRMT6; Nucleolar trafficking