Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1863, Issue 2, Pages 254-262Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2015.11.019
Keywords
Nudeolar trafficking; Methyltransferase PRMT6; HIV-1 Tat; HIV-1 Rev; HTLV-1 Rex
Categories
Funding
- National Health and Medical Research Council Australia [384105/APP1002486, 143710, 389826]
- Australian Centre for HIV and Hepatitis Virology [2015-13]
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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 nudeolar retention. (C) 2015 Elsevier B.V. All rights reserved.
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