title: Identification of the methylation preference region in heterogeneous nuclear ribonucleoprotein K by protein arginine methyltransferase 1 and its implication in regulating nuclear/cytoplasmic distribution.
abstract: Protein arginine methylation plays crucial roles in numerous cellular processes. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein participating in a variety of cellular functions including transcription and RNA processing. HnRNP K is methylated at multiple sites in the glycine- and arginine-rich (RGG) motif. Using various RGG domain deletion mutants of hnRNP K as substrates, here we show by direct methylation assay that protein arginine methyltransferase 1 (PRMT1) methylated preferentially in a.a. 280-307 of the RGG motif. Kinetic analysis revealed that deletion of a.a. 280-307, but not a.a. 308-327, significantly inhibited rate of methylation. Importantly, nuclear localization of hnRNP K was significantly impaired in mutant hnRNP K lacking the PRMT1 methylation region or upon pharmacological inhibition of methylation. Together our results identify preferred PRMT1 methylation sequences of hnRNP K by direct methylation assay and implicate a role of arginine methylation in regulating intracellular distribution of hnRNP K.
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Yuan-I
authors.initials: YI
authors.lastname: Chang
authors.forename: Sheng-Chieh
authors.initials: SC
authors.lastname: Hsu
authors.forename: Gar-Yang
authors.initials: GY
authors.lastname: Chau
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
authors.forename: Jung-Sung
authors.initials: JS
authors.lastname: Sung
authors.forename: Wei-Kai
authors.initials: WK
authors.lastname: Hua
authors.forename: Wey-Jinq
authors.initials: WJ
authors.lastname: Lin
mesh_terms: D001120:Arginine / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012097:Repressor Proteins; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases