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Discrimination of eIF4A isoforms by protein arginine methyltransferase 1 (PRMT1)
Author(s) -
Tahara Stanley M,
Acuna Marcela
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a109-d
Subject(s) - eif4a1 , eif4a , helicase , eukaryotic initiation factor , biology , rna helicase a , eukaryotic translation , eif4g , methylation , biochemistry , rna , messenger rna , ribosome , dna , translation (biology) , gene
Initiation factor eIF4A is the prototype of DExD/H RNA helicase superfamily 2. It has RNA‐dependent ATPase activity and is responsible for relaxing mRNA secondary structure during initiation of protein synthesis. We found that PRMT1 methylated eIF4A1 at Arg 362, within conserved helicase motif VI, in vitro . Since this residue is retained among eIF4A orthologs, in all eukaryotic species, we examined methyl acceptor activities of other eIF4A isoforms with PRMT1. eIF4A3 has the motif VI sequence of: HRIG R SGRYG vs. HRIG R GGRFG for eIF4A1 and eIF4A2. However, eIF4A3 was found not to be a substrate of PRMT1. Since motif VI of eIF4A3 differs from eIF4A1/2 by a single Ser residue behind the central Arg ( R ), we tested whether substitution of Gly363 by Ser in eIF4A1 affected methylation. eIF4A1(G363S) could not be methylated; therefore, this single amino acid change was sufficient to antagonize recognition by PRMT1 and explains why eIF4A3 can not be methylated. eIF4A1 methylation inhibited interaction with eIF4G; potentially interfering with eIF4F assembly. Furthermore, methylation of eIF4A1 inhibited ATPase activity by greater than 50%. This was significant because Arg362 is an important residue for ATP hydrolysis and RNA helicase activities. We hypothesize methylation of eIF4A is potentially of regulatory significance given the precise modification of eIF4A by PRMT1. Furthermore, the inability of eIF4A3 to be methylated may be related to the finding that it is not important in translation but participates in RNA processing. Thus, cellular conditions that foster methylation and modulation of eIF4A1/2 activities would not result in eIF4A3 methylation.