Alternative splicing yields protein arginine methyltransferase 1 isoforms with distinct activity, substrate specificity, and subcellular localization

J Biol Chem. 2007 Nov 9;282(45):33009-21. doi: 10.1074/jbc.M704349200. Epub 2007 Sep 11.

Abstract

PRMT1 is the predominant member of a family of protein arginine methyltransferases (PRMTs) that have been implicated in various cellular processes, including transcription, RNA processing, and signal transduction. It was previously reported that the human PRMT1 pre-mRNA was alternatively spliced to yield three isoforms with distinct N-terminal sequences. Close inspection of the genomic organization in the 5'-end of the PRMT1 gene revealed that it can produce up to seven protein isoforms, all varying in their N-terminal domain. A detailed biochemical characterization of these variants revealed that unique N-terminal sequences can influence catalytic activity as well as substrate specificity. In addition, our results uncovered the presence of a functional nuclear export sequence in PRMT1v2. Finally, we find that the relative balance of PRMT1 isoforms is altered in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Conserved Sequence
  • Exons / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Genome, Human / genetics
  • Health
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Leucine / genetics
  • Leucine / metabolism
  • Molecular Sequence Data
  • Protein-Arginine N-Methyltransferases / chemistry
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Substrate Specificity

Substances

  • Isoenzymes
  • Repressor Proteins
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases
  • Leucine