Human isoleucyl-tRNA synthetase: sequence of the cDNA, alternative mRNA splicing, and the characteristics of an unusually long C-terminal extension.
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 5'-UTR, 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.
Nichols
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RC
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Raben
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N
Boerkoel
C F
CF
Plotz
P H
PH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007533:Isoleucine-tRNA Ligase / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017421:Sequence Analysis
D018076:DNA, Complementary; D012333:RNA, Messenger; D007533:Isoleucine-tRNA Ligase