Arginine methylation plays crucial roles in many cellular functions including signal transduction, RNA transcription, and regulation of gene expression. Protein arginine methyltransferase 8 (PRMT8), a unique brain-specific protein, is localized to the plasma membrane. However, the detailed molecular mechanisms underlying PRMT8 plasma membrane targeting remain unclear. Here, we demonstrate that the N-terminal 20 amino acids of PRMT8 are sufficient for plasma membrane localization and that oligomerization enhances membrane localization. The basic amino acids, combined with myristoylation within the N-terminal 20 amino acids of PRMT8, are critical for plasma membrane targeting. We also found that substituting Gly-2 with Ala [PRMT8(G2A)] or Cys-9 with Ser [PRMT8(C9S)] induces the formation of punctate structures in the cytosol or patch-like plasma membrane localization, respectively. Impairment of PRMT8 oligomerization/dimerization by Cterminal deletion induces PRMT8 mis-localization to the mitochondria, prevents the formation of punctate structures by PRMT8(G2A), and inhibits PRMT8(C9S) patch-like plasma membrane localization. Overall, these results suggest that oligomerization/dimerization plays several roles in inducing the efficient and specific plasma membrane localization of PRMT8. [BMB Reports 2019; 52(10): 601-606].
Conflict of interest statement
The authors have no conflicting interests.
PRMT8, a New Membrane-Bound Tissue-Specific Member of the Protein Arginine Methyltransferase FamilyJ Lee et al. J Biol Chem 280 (38), 32890-6. PMID 16051612.Protein arginine methylation is a common post-translational modification that has been implicated in signal transduction, RNA processing, transcriptional regulation, and …
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Regulation of Protein Arginine Methyltransferase 8 (PRMT8) Activity by Its N-terminal DomainJ Sayegh et al. J Biol Chem 282 (50), 36444-53. PMID 17925405.Human protein arginine methyltransferase PRMT8 has been recently described as a type I enzyme in brain that is localized to the plasma membrane by N-terminal myristoylati …
Arginine Methyltransferase PRMT8 Provides Cellular Stress Tolerance in Aging MotoneuronsZ Simandi et al. J Neurosci 38 (35), 7683-7700. PMID 30054395.Aging contributes to cellular stress and neurodegeneration. Our understanding is limited regarding the tissue-restricted mechanisms providing protection in postmitotic ce …
Automethylation of Protein Arginine Methyltransferase 8 (PRMT8) Regulates Activity by Impeding S-adenosylmethionine SensitivityMB Dillon et al. J Biol Chem 288 (39), 27872-80. PMID 23946480.Protein arginine methyltransferase (PRMT) 8 is unique among the PRMTs, as it has a highly restricted tissue expression pattern and an N terminus that contains two automet …
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