TY - JOUR
T1 - Human isoleucyl-tRNA synthetase
T2 - Sequence of the cDNA, alternative mRNA splicing, and the characteristics of an unusually long C-terminal extension
AU - Nichols, Ralph C.
AU - Raben, Nina
AU - Boerkoel, Cornelius F.
AU - Plotz, Paul H.
PY - 1995/4/3
Y1 - 1995/4/3
N2 - 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.
AB - 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.
KW - autoantigen
KW - Gene cloning
KW - high-molecular-weight complex
KW - interferon-stimulated response element
KW - polymerase chain reaction
KW - repeat motif
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U2 - 10.1016/0378-1119(94)00634-5
DO - 10.1016/0378-1119(94)00634-5
M3 - Article
C2 - 7721108
AN - SCOPUS:0028957824
SN - 0378-1119
VL - 155
SP - 299
EP - 304
JO - Gene
JF - Gene
IS - 2
ER -