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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

Research highlights: {yields} Verifying by direct methylation assay the substrate sites of PRMT1 in the hnRNP K protein. {yields} Identifying the preferred PMRT1 methylation regions in hnRNP K by kinetic analysis. {yields} Linking methylation in regulating nuclear localization of hnRNP K. -- 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:
;  [1];  [2];  [3];  [1];  [3];  [4];  [1];  [1];  [3]
  1. Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan (China)
  2. Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan (China)
  3. (China)
  4. Taipei City Hospital, Yang-Ming Branch, Taipei 111, Taiwan (China)
Publication Date:
OSTI Identifier:
22204766
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 404; Journal Issue: 3; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOSINE; ARGININE; GLYCINE; INHIBITION; METHIONINE; METHYL TRANSFERASES; METHYLATION; MUTANTS; PHOSPHOTRANSFERASES; RNA PROCESSING; SUBSTRATES; TRANSCRIPTION

Citation Formats

Chang, Yuan-I, Hsu, Sheng-Chieh, Chau, Gar-Yang, Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, Huang, Chi-Ying F., Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan, Sung, Jung-Sung, Hua, Wei-Kai, Lin, Wey-Jinq, E-mail: wjlin@ym.edu.tw, and Department of Education and Research, Taipei City Hospital, Taipei 103, Taiwan. Identification of the methylation preference region in heterogeneous nuclear ribonucleoprotein K by protein arginine methyltransferase 1 and its implication in regulating nuclear/cytoplasmic distribution. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2010.12.076.
Chang, Yuan-I, Hsu, Sheng-Chieh, Chau, Gar-Yang, Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, Huang, Chi-Ying F., Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan, Sung, Jung-Sung, Hua, Wei-Kai, Lin, Wey-Jinq, E-mail: wjlin@ym.edu.tw, & Department of Education and Research, Taipei City Hospital, Taipei 103, Taiwan. Identification of the methylation preference region in heterogeneous nuclear ribonucleoprotein K by protein arginine methyltransferase 1 and its implication in regulating nuclear/cytoplasmic distribution. United States. doi:10.1016/J.BBRC.2010.12.076.
Chang, Yuan-I, Hsu, Sheng-Chieh, Chau, Gar-Yang, Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, Huang, Chi-Ying F., Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan, Sung, Jung-Sung, Hua, Wei-Kai, Lin, Wey-Jinq, E-mail: wjlin@ym.edu.tw, and Department of Education and Research, Taipei City Hospital, Taipei 103, Taiwan. Fri . "Identification of the methylation preference region in heterogeneous nuclear ribonucleoprotein K by protein arginine methyltransferase 1 and its implication in regulating nuclear/cytoplasmic distribution". United States. doi:10.1016/J.BBRC.2010.12.076.
@article{osti_22204766,
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},
author = {Chang, Yuan-I and Hsu, Sheng-Chieh and Chau, Gar-Yang and Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan and Huang, Chi-Ying F. and Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan and Sung, Jung-Sung and Hua, Wei-Kai and Lin, Wey-Jinq, E-mail: wjlin@ym.edu.tw and Department of Education and Research, Taipei City Hospital, Taipei 103, Taiwan},
abstractNote = {Research highlights: {yields} Verifying by direct methylation assay the substrate sites of PRMT1 in the hnRNP K protein. {yields} Identifying the preferred PMRT1 methylation regions in hnRNP K by kinetic analysis. {yields} Linking methylation in regulating nuclear localization of hnRNP K. -- 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.},
doi = {10.1016/J.BBRC.2010.12.076},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 404,
place = {United States},
year = {Fri Jan 21 00:00:00 EST 2011},
month = {Fri Jan 21 00:00:00 EST 2011}
}