Wide Cross-species Aminoacyl-tRNA Synthetase Replacement in Vivo: Yeast Cytoplasmic Alanine Enzyme Replaced by Human Polymyositis Serum Antigen

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 May 23

PMID 7761427

Citations 17

Authors

T L Ripmaster

K Shiba

P Schimmel

Affiliations

Soon will be listed here.

Abstract

Because of variations in tRNA sequences in evolution, tRNA synthetases either do not acylate their cognate tRNAs from other organisms or execute misacylations which can be deleterious in vivo. We report here the cloning and primary sequence of a 958-aa Saccharomyces cerevisiae alanyl-tRNA synthetase. The enzyme is a close homologue of the human and Escherichia coli enzymes, particularly in the region of the primary structure needed for aminoacylation of RNA duplex substrates based on alanine tRNA acceptor stems with a G3.U70 base pair. An ala1 disrupted allele demonstrated that the gene is essential and that, therefore, ALA1 encodes an enzyme required for cytoplasmic protein synthesis. Growth of cells harboring the ala1 disrupted allele was restored by a cDNA clone encoding human alanyl-tRNA synthetase, which is a serum antigen for many polymyositis-afflicted individuals. The human enzyme in extracts from rescued yeast was detected with autoimmune antibodies from a polymyositis patient. We conclude that, in spite of substantial differences between human and yeast tRNA sequences in evolution, strong conservation of the G3.U70 system of recognition is sufficient to yield accurate aminoacylation in vivo across wide species distances.

Citing Articles

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References

Rose M, Novick P, Thomas J, Botstein D, Fink G . A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987; 60(2-3):237-43. DOI: 10.1016/0378-1119(87)90232-0. View

Shiba K, Schimmel P, MOTEGI H, Noda T . Human glycyl-tRNA synthetase. Wide divergence of primary structure from bacterial counterpart and species-specific aminoacylation. J Biol Chem. 1994; 269(47):30049-55. View

Hou Y, Schimmel P . A simple structural feature is a major determinant of the identity of a transfer RNA. Nature. 1988; 333(6169):140-5. DOI: 10.1038/333140a0. View

Park S, Schimmel P . Evidence for interaction of an aminoacyl transfer RNA synthetase with a region important for the identity of its cognate transfer RNA. J Biol Chem. 1988; 263(32):16527-30. View

Hill K, Schimmel P . Evidence that the 3' end of a tRNA binds to a site in the adenylate synthesis domain of an aminoacyl-tRNA synthetase. Biochemistry. 1989; 28(6):2577-86. DOI: 10.1021/bi00432a035. View

Sikorski R, Hieter P . A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989; 122(1):19-27. PMC: 1203683. DOI: 10.1093/genetics/122.1.19. View

Targoff I, Arnett F, Berman L, OBrien C, Reichlin M . Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease. J Clin Invest. 1989; 84(1):162-72. PMC: 303966. DOI: 10.1172/JCI114136. View

Soll D . Cloning and characterization of the gene coding for cytoplasmic seryl-tRNA synthetase from Saccharomyces cerevisiae. Nucleic Acids Res. 1987; 15(5):1887-904. PMC: 340606. DOI: 10.1093/nar/15.5.1887. View

Schimmel P . Aminoacyl tRNA synthetases: general scheme of structure-function relationships in the polypeptides and recognition of transfer RNAs. Annu Rev Biochem. 1987; 56:125-58. DOI: 10.1146/annurev.bi.56.070187.001013. View

10.

Edwards H, Schimmel P . An E. coli aminoacyl-tRNA synthetase can substitute for yeast mitochondrial enzyme function in vivo. Cell. 1987; 51(4):643-9. DOI: 10.1016/0092-8674(87)90133-4. View

11.

Bunn C, Mathews M . Autoreactive epitope defined as the anticodon region of alanine transfer RNA. Science. 1987; 238(4830):1116-9. DOI: 10.1126/science.2446387. View

12.

Chatton B, Walter P, Ebel J, Lacroute F, Fasiolo F . The yeast VAS1 gene encodes both mitochondrial and cytoplasmic valyl-tRNA synthetases. J Biol Chem. 1988; 263(1):52-7. View

13.

Plotz P, Dalakas M, Leff R, Love L, Miller F, Cronin M . Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. Ann Intern Med. 1989; 111(2):143-57. DOI: 10.7326/0003-4819-111-2-143. View

14.

Hou Y, Schimmel P . Evidence that a major determinant for the identity of a transfer RNA is conserved in evolution. Biochemistry. 1989; 28(17):6800-4. DOI: 10.1021/bi00443a003. View

15.

Bedouelle H, Guez V, Vidal-Cros A, Hermann M . Overproduction of tyrosyl-tRNA synthetase is toxic to Escherichia coli: a genetic analysis. J Bacteriol. 1990; 172(7):3940-5. PMC: 213377. DOI: 10.1128/jb.172.7.3940-3945.1990. View

16.

Eriani G, Delarue M, Poch O, Gangloff J, Moras D . Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature. 1990; 347(6289):203-6. DOI: 10.1038/347203a0. View

17.

Cusack S, Berthet-Colominas C, Hartlein M, Nassar N, Leberman R . A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A. Nature. 1990; 347(6290):249-55. DOI: 10.1038/347249a0. View

18.

Scaringe S, Francklyn C, Usman N . Chemical synthesis of biologically active oligoribonucleotides using beta-cyanoethyl protected ribonucleoside phosphoramidites. Nucleic Acids Res. 1990; 18(18):5433-41. PMC: 332221. DOI: 10.1093/nar/18.18.5433. View

19.

CHANG P, Dignam J . Primary structure of alanyl-tRNA synthetase and the regulation of its mRNA levels in Bombyx mori. J Biol Chem. 1990; 265(34):20898-906. View

20.

Scaringe S, Usman N, Schimmel P . Enzymatic aminoacylation of single-stranded RNA with an RNA cofactor. Proc Natl Acad Sci U S A. 1991; 88(1):209-13. PMC: 50779. DOI: 10.1073/pnas.88.1.209. View