Critical role for arginine methylation in adenovirus-infected cells.
During the late stages of adenovirus infection, the 100K protein (100K) inhibits the translation of cellular messages in the cytoplasm and regulates hexon trimerization and assembly in the nucleus. However, it is not known how it switches between these two functions. Here we show that 100K is methylated on arginine residues at its C terminus during infection and that this region is necessary for binding PRMT1 methylase. Methylated 100K is exclusively nuclear. Mutation of the third RGG motif (amino acids 741 to 743) prevents localization to the nucleus during infection, suggesting that methylation of that sequence is important for 100K shuttling. Treatment of infected cells with methylation inhibitors inhibits expression of late structural proteins. These data suggest that arginine methylation of 100K is necessary for its localization to the nucleus and is a critical cellular function necessary for productive adenovirus infection.
Iacovides
Demetris C
DC
UCSF Comprehensive Cancer Center, 2340 Sutter St., San Francisco, CA 94115, USA.
O'Shea
Clodagh C
CC
Oses-Prieto
Juan
J
Burlingame
Alma
A
McCormick
Frank
F
D000256:Adenoviridae / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D006801:Humans; D008745:Methylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000096:biosynthesis
C477284:L4-100K protein, adenovirus type 5; D012097:Repressor Proteins; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases