Isolation of a novel antibody, which precipitates ribonucleoprotein complex containing threonine tRNA from a patient with polymyositis

Okada, Norihiro; Mukai, Ryozaburo; Harada, Fumio; Kabashima, Teizo; Nakao, Yasuro; Yamane, Kazuhide; Ohshima, Yasumi; Sakamoto, Kazuichi; Itoh, Michiyasu; Kashiwagi, Hirokazu; Hamaguchi, Hideo

doi:10.1111/j.1432-1033.1984.tb08022.x

Cited by 31 publications

(6 citation statements)

References 16 publications

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“…The reactive antigens are usually tRNA-associated proteins; in only a few cases are they the tRNAs themselves (4,6). Some of these protein antigens have been identified as aminoacyl-tRNA synthetases (3,(6)(7)(8)(9)(10).…”

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confidence: 99%

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Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Gelpí

Sontheimer

Rodríguez-Sánchez

1992

Proc. Natl. Acad. Sci. U.S.A.

142

114

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We describe an autoantibody specificity present in a subgroup of patients with a severe form of autoimmune chronic active hepatitis. These antibodies precipitate a 90-nucleotide RNA from human whole cell extracts and recognize a 48-kDa polypeptide in immunoblotting assays. The RNA is a UGA suppressor serine tRNA that carries selenocysteine (tRNAlserJs'¢), as shown by sequence analysis. The protein does not appear to be seryl-tRNA synthetase; rather, it is an excellent candidate for a factor involved in cotranslational selenocysteine incorporation in human cells.Autoantibodies reactive with cellular constituents are often detected in sera from patients with autoimmune disease. Autoantibodies that immunoprecipitate tRNA have been detected primarily in sera from patients with polymyositis (1-3) and, less frequently, in patients with systemic lupus erythematosus (4) and scleroderma (5). The reactive antigens are usually tRNA-associated proteins; in only a few cases are they the tRNAs themselves (4, 6). Some of these protein antigens have been identified as aminoacyl-tRNA synthetases (3, 6-10).Other well-characterized components of the protein synthetic machinery [for example, ribosomes (11), 5S ribonucleoprotein (12), and elongation factor la (13)] also act as autoantigens. One translational event, the incorporation of selenocysteine into a growing polypeptide chain, is not well-understood in eukaryotes, and to our knowledge, the factors involved in this process have not been implicated in autoimmunity. The synthesis of selenoproteins in Escherichia coli involves several reactions (for review, see ref. 14). Briefly, selenocysteine incorporation is cotranslational and requires an unusual suppressor aminoacyl-tRNA (selenocysteyl-tRNAsec, where Sec is selenocysteine) and a specific translation factor (the product of the selB gene) that substitutes for elongation factor Tu. Insertion is directed by certain UGA triplets that in other contexts act as termination codons. tRNASec is initially charged with serine to form seryltRNASec and is then converted to selenocysteyl-tRNAsec by the action of the selA (selenocysteine synthase) and selD gene products. In mammalian cells, selenocysteine incorporation also occurs at specific UGA codons, and a suppressor serine tRNA that carries selenocysteine (tRNA[Serlsec) has been detected (15). However, complete elucidation of the eukaryotic pathway (and identification of the factors involved) has not yet been achieved.Here we report that an RNA-protein complex is the target of an autoantibody specificity found in the sera of a subset of patients with autoimmune chronic active hepatitis (AI-CAH). The RNA corresponds to a previously identified human suppressor serine tRNA, and the antigenic protein may be a factor involved in the pathway of cotranslational incorporation of selenocysteine into specific polypeptide chains.MATERIALS AND METHODS Subjects. Sera from 35 patients with AI-CAH were collected over a period of 4 years at the Sant Pau and Valle Hebron Hospitals in Barcelona. ...

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confidence: 99%

“…All values are for 1:10 serum dilutions; cpm is the amount of radioactivity converted to trichloroacetic acid-precipitable form. The positive control sera [anti-isoleucyl-tRNA synthetase (10), anti-PL-7 (anti-threonyl-tRNA synthetase) (8,9), and anti-Jol (anti-histidyl-tRNA synthetase) (3)] are specific for their particular synthetases.…”

mentioning

confidence: 99%

Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Gelpí

Sontheimer

Rodríguez-Sánchez

1992

Proc. Natl. Acad. Sci. U.S.A.

142

114

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“…2, specific immunoprecipitation of tRNA by KJ serum could not be demonstrated. Previous studies have consistently found that autoantibodies to any of the five antigenic aminoacyl-tRNA synthetases immunoprecipitate their respective cognate tRNAs (4,(22)(23)(24)(25)32). This is demonstrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…There is a distinct enzyme in the cytoplasm for each amino acid (as well as a second in the mitochondria). Antibodies to two of the other aminoacyl-tRNA synthetases have been reported in myositis patients, anti-threonyl-tRNA synthetase (anti-PL-7) (22,23) and anti-alanyl-tRNA synthetase (anti-PL-12) (24). Although exceptions occurred, almost all the patients in whom these antibodies were found had myositis (9,22,24), and most also had ILD (9).…”

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confidence: 98%

Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease.

Targoff¹,

Arnett²,

Berman³

et al. 1989

J. Clin. Invest.

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Antibodies to aminoacyl-tRNA synthetases (anti-Jo-i, anti-PL-7, anti-PL-12) have been found in the serum of some patients with polymyositis (PM). Patients with these antibodies have an unusually high rate of interstitial lung disease (ILD) in association with their PM. Two patients (K.J. and B.T.) with severe ILD and PM were found to have antibodies to a cytoplasmic antigen, but tests to determine whether the antigen was an aminoacyl-tRNA synthetase were negative, including tests of LJ serum for inhibitory effects on the 20 synthetases. KJ immunoprecipitates did not contain tRNA, in contrast to antisynthetase sera. When IgG samples were added to a reticulocyte in vitro translation system at a concentration of 0.3 mg/mi, KJ IgG inhibited globin mRNA translation by 98%, while anti-Jo-i IgG inhibited 62% and normal IgG had little effect. Thus, both anti-LJ and the antisynthetases are directed at antigens that are involved in translation and protein synthesis, and both are associated with the syndrome of lung disease and PM. This syndrome may be associated with antibodies to translation-related proteins in general, which may have implications for the link of PM and enteroviruses, which are mRNA viruses.

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“…During the last three decades it turned out that some diseases which are classically categorized as rheumatic diseases are connected with formation of antibodies against nucleic acids (Okada et al, 1984) and proteins of the own organism (Marguerie etal., 1990;Sontheimer et al, 1992). Among the diverse species of autoantibodies a few immunogobulins were detected which reacted with aminoacyl-tRNA synthetases.…”

Section: Threonyl-trna Synthetase and Autoimmune Diseasesmentioning

confidence: 99%

Review

1995

Biological Chemistry Hoppe-Seyler

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One of the salient features of the mammalian genome is the vast excess of DNA without obvious function, such as repetitive DNAs, spacers, and introns. In recent years, microsatellites, which include short triplet repeats (mostly CAGn and CGGn) and dinucleotide repeats (notably CAn) have gained widespread attention, along with minisatellites which consist of somewhat longer repeat units. Micro- and minisatellites, collectively called variable number tandem repeats (VNTRs), can be highly unstable and display an amazing degree of polymorphism. This property is exploited for gene mapping, for tumor diagnosis, and in forensic medicine. Undue expansion of gene-associated microsatellites is also responsible for some severe genetic diseases, such as fragile X syndrome. Most or all of these diseases are caused by expansion of CAG and CGG triplets. Within protein-coding regions these triplets usually code for polymers of glutamine, serine, alanine or proline. Physiologically, such amino acid repeats are often found in transcription factors and can increase or decrease their activity, depending on the repeat number. Alone or in conjunction with DNA methylation, such repeats may offer a unique opportunity for subtle, semi-stable modulation of gene activity. Also, at least in some plants and perhaps other organisms, a quasi-Lamarckian inheritance is mediated by repetitive DNA. Generally, repetitive DNA sequences, whether represented by short or by long DNA segments, may be beneficial for the evolution of a species.

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Isolation of a novel antibody, which precipitates ribonucleoprotein complex containing threonine tRNA from a patient with polymyositis

Cited by 31 publications

References 16 publications

Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease.

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