Human isoleucyl-tRNA synthetase: Sequence of the cDNA, alternative mRNA splicing, and the characteristics of an unusually long C-terminal extension

Ralph C. Nichols, Nina Raben, Cornelius F. Boerkoel, Paul H. Plotz

Research output: Contribution to journalArticle

Abstract

The human isoleucyl-tRNA synthetase (IRS)-encoding cDNA, whose primary structure we report here, has an open reading frame (ORF) which encodes a protein of 1262 amino acids (aa) with strong homology to IRS from yeast (53.5%) and Tetrahymena (51.0%) and contains all the major consensus motifs of class-I hydrophobic amino-acyl-tRNA synthetases (aaRS; MRS, LRS, VRS, IRS). However, the human enzyme has an unusually long C-terminal extension composed, in part, of a twice-repeated motif which shows no homology to any reported protein. We also report the presence of a coiled-coil-like motif in the C-terminal half of the protein. The mRNA has an additional exon in the 5'-untranslated region (UTR) which is alternatively spliced, giving rise to two types of mRNA, both of which are expressed in several human tissues. The longer of the two transcripts contains predicted secondary structure in the 5-UTR which may reduce the translational efficiency of this mRNA. Two possible regulatory elements in the 5UTR, an interferon-stimulated response element (ISRE)-like sequence and a short ORF, have been identified. Because human IRS has previously been shown to be the target of antibodies in autoimmune disease, we discuss the role of protein structural features in the development of an autoimmune response to IRS.

Original languageEnglish (US)
Pages (from-to)299-304
Number of pages6
JournalGene
Volume155
Issue number2
DOIs
StatePublished - Apr 3 1995
Externally publishedYes

Keywords

  • autoantigen
  • Gene cloning
  • high-molecular-weight complex
  • interferon-stimulated response element
  • polymerase chain reaction
  • repeat motif

ASJC Scopus subject areas

  • Genetics

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