DOI Page / Citation link:
https://doi.org/10.11588/diglit.48120#0067
Abstracts
49
Aminoacyl-tRNA Synthetases: an Overview
M. B. Mathews
Cold Spring Harbor Laboratory, P.O. Box 100, Cold Spring Harbor, New York,
N. Y. 11724, USA
Antibodies directed against tRNA-related antigens are common in the inflam-
matory muscle diseases, polymyositis and dermatomyositis, but are relatively rare
in other autoimmune diseases such as lupus and rheumatoid arthritis. Myositis
patients also possess antibodies directed against nuclear antigens, such as RNP.
The overall frequency of autoantibodies in myositis patients is approximately
90%. About a third of myositis patients carry antibodies against tRNA-related
antigens, and this frequency is doubled in patients who also suffer from in-
terstitial lung disease. Other kinds of autoantibodies, directed against DNA bind-
ing (Ku) and unidentified (Mi-2 and PM-Scl) proteins, are also characteristic of
myositis sera. To a limited extent, these antibodies seem to be characteristic of
subsets of patients, although the clinical basis for this specificity remains obscure.
Most of the tRNA-related antigens are aminoacyl-tRNA synthetases. These
enzymes catalyze the charging of tRNA with its cognate aminoacid. There are
twenty such enzymes, each specific for an individual aminoacid and able to
recognize all of the tRNAs that accept this aminoacid. During the course of the
reaction a molecule of ATP is hydrolyzed to AMP and pyrophosphate. In
myositis, about 25% of patients contain antibodies of the Jo-1 class, specific for
histidyl-tRNA synthetase. Jo-1 antibody immunoprecipitates the synthetase enz-
mye together with associated tRNAHls but no antibodies have been detected that
are specific for the tRNA itself. The antibodies inhibit aminoacylation of tRNA
with histidine, and accordingly block protein synthesis in a rabbit reticulocyte cell-
free system. Antibodies directed against other synthetases are considerably rarer.
PL-7 antibody reacts with threonyl-tRNA synthetase and is present in approx-
imately 6% of myositis patients. Like Jo-1, PD7 antibody is directed against the
enzyme and coprecipitates the cognate tRNA. Interestingly, an experimental an-
tibody raised against the same enzyme fails to coprecipitate tRNAThr, suggesting
that the rabbit antibody either reacts with a denatured form of the protein in-
capable of binding tRNA or, alternatively, blocks tRNA binding to the enzyme.
A third specificity, known as PL-12, precipitates both alanyl-tRNA and tRNAAla
but differs from the two previous specificities in two ways. The synthetase and the
tRNA are recognized separately by autoantibodies directed against the protein
and RNA components, and antibodies against the synthetase fail to coprecipitate
the tRNA. The site on the tRNA that is recognized by the anti-tRNAAla compo-
nent has been identified as the anticodon stem and loop structure. PL-12 antibody
is also found in about 5% of myositis patients. Additional specificities that have
49
Aminoacyl-tRNA Synthetases: an Overview
M. B. Mathews
Cold Spring Harbor Laboratory, P.O. Box 100, Cold Spring Harbor, New York,
N. Y. 11724, USA
Antibodies directed against tRNA-related antigens are common in the inflam-
matory muscle diseases, polymyositis and dermatomyositis, but are relatively rare
in other autoimmune diseases such as lupus and rheumatoid arthritis. Myositis
patients also possess antibodies directed against nuclear antigens, such as RNP.
The overall frequency of autoantibodies in myositis patients is approximately
90%. About a third of myositis patients carry antibodies against tRNA-related
antigens, and this frequency is doubled in patients who also suffer from in-
terstitial lung disease. Other kinds of autoantibodies, directed against DNA bind-
ing (Ku) and unidentified (Mi-2 and PM-Scl) proteins, are also characteristic of
myositis sera. To a limited extent, these antibodies seem to be characteristic of
subsets of patients, although the clinical basis for this specificity remains obscure.
Most of the tRNA-related antigens are aminoacyl-tRNA synthetases. These
enzymes catalyze the charging of tRNA with its cognate aminoacid. There are
twenty such enzymes, each specific for an individual aminoacid and able to
recognize all of the tRNAs that accept this aminoacid. During the course of the
reaction a molecule of ATP is hydrolyzed to AMP and pyrophosphate. In
myositis, about 25% of patients contain antibodies of the Jo-1 class, specific for
histidyl-tRNA synthetase. Jo-1 antibody immunoprecipitates the synthetase enz-
mye together with associated tRNAHls but no antibodies have been detected that
are specific for the tRNA itself. The antibodies inhibit aminoacylation of tRNA
with histidine, and accordingly block protein synthesis in a rabbit reticulocyte cell-
free system. Antibodies directed against other synthetases are considerably rarer.
PL-7 antibody reacts with threonyl-tRNA synthetase and is present in approx-
imately 6% of myositis patients. Like Jo-1, PD7 antibody is directed against the
enzyme and coprecipitates the cognate tRNA. Interestingly, an experimental an-
tibody raised against the same enzyme fails to coprecipitate tRNAThr, suggesting
that the rabbit antibody either reacts with a denatured form of the protein in-
capable of binding tRNA or, alternatively, blocks tRNA binding to the enzyme.
A third specificity, known as PL-12, precipitates both alanyl-tRNA and tRNAAla
but differs from the two previous specificities in two ways. The synthetase and the
tRNA are recognized separately by autoantibodies directed against the protein
and RNA components, and antibodies against the synthetase fail to coprecipitate
the tRNA. The site on the tRNA that is recognized by the anti-tRNAAla compo-
nent has been identified as the anticodon stem and loop structure. PL-12 antibody
is also found in about 5% of myositis patients. Additional specificities that have