Arginine methylation increases the stability of human immunodeficiency virus type 1 Tat

Haran Sivakumaran, Armando van der Horst, Alex J Fulcher, Ann Apolloni, Min-Hsuan Lin, David Andrew Jans, David Harrich

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)


Arginine methylation of human immunodeficiency virus type 1 (HIV-1) Tat protein downregulates its key function in viral gene transactivation. The fate of methylated Tat is unknown, so it is unclear whether methylated Tat is degraded or persists in the cell for additional functions. Here we show that the arginine methyltransferase PRMT6 increases Tat protein half-life by 4.7-fold. Tat stabilization depends on the catalytic activity of PRMT6 and requires arginine methylation within the Tat basic domain. HIV-1 Rev, in contrast, which is also methylated by PRMT6, is completely refractory to the stabilizing effect. Proteasome inhibition and silencing experiments demonstrated that Tat can be degraded by a REGgamma-independent proteasome, against which PRMT6 appears to act to increase Tat half-life. Our data reveal a proteasome-dependent Tat degradation pathway that is inhibited by arginine methylation. The stabilizing action of PRMT6 could allow Tat to persist within the cell and extracellular environment and thereby enable functions implicated in AIDS-related cancer, neurodegeneration and T cell death.
Original languageEnglish
Pages (from-to)11694 - 11703
Number of pages10
JournalJournal of Virology
Issue number22
Publication statusPublished - 2009

Cite this