WARS (gene) explained

Tryptophanyl-tRNA synthetase, cytoplasmic is an aminoacyl-tRNA synthetase enzyme that attaches the amino acid tryptophan to its cognate tRNA. In humans, it is encoded by the WARS gene.^{[1] [2] [3]}

Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. Tryptophanyl-tRNA synthetase (WARS) catalyzes the aminoacylation of tRNA(trp) with tryptophan and is induced by interferon. Tryptophanyl-tRNA synthetase belongs to the class I tRNA synthetase family. Four transcript variants encoding two different isoforms have been found for this gene.^[3]

Phenylalanine Incorporation

Although WARS1 classically aminoacylates tryptophan, during states tryptophan depeletion, this enzyme has been observed to activate both tryptophan and phenylalanine.^[4]

Further reading

• Ewalt KL, Schimmel P . Activation of angiogenic signaling pathways by two human tRNA synthetases . Biochemistry . 41 . 45 . 13344–13349 . November 2002 . 12416978 . 10.1021/bi020537k .
• Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J . Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes . Electrophoresis . 13 . 12 . 960–969 . December 1992 . 1286667 . 10.1002/elps.11501301199 . 41855774 .
• Bange FC, Flohr T, Buwitt U, Böttger EC . An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase . FEBS Letters . 300 . 2 . 162–166 . March 1992 . 1373391 . 10.1016/0014-5793(92)80187-L . 35675265 .
• Rubin BY, Anderson SL, Xing L, Powell RJ, Tate WP . Interferon induces tryptophanyl-tRNA synthetase expression in human fibroblasts . The Journal of Biological Chemistry . 266 . 36 . 24245–24248 . December 1991 . 1761529 . 10.1016/S0021-9258(18)54219-8 . free .
• Sudomoina MA, Zinovieva OL, Kisselev LL . Cloning and nucleotide sequence of the structural gene encoding for human tryptophanyl-tRNA synthetase . Gene . 109 . 2 . 291–296 . December 1991 . 1765274 . 10.1016/0378-1119(91)90624-K .
• Frolova LY, Grigorieva AY, Sudomoina MA, Kisselev LL . The human gene encoding tryptophanyl-tRNA synthetase: interferon-response elements and exon-intron organization . Gene . 128 . 2 . 237–245 . June 1993 . 7685728 . 10.1016/0378-1119(93)90568-N .
• Popenko VI, Cherny NE, Beresten SF, Ivanova JL, Filonenko VV, Kisselev LL . Immunoelectron microscopic location of tryptophanyl-tRNA synthetase in mammalian, prokaryotic and archaebacterial cells . European Journal of Cell Biology . 62 . 2 . 248–258 . December 1993 . 7925483 .
• Børglum AD, Flint T, Tommerup N, Fleckner J, Justesen J, Kruse TA . Assignment of the human tryptophanyl-tRNA synthetase gene (WARS) to chromosome 14q32.2 --> q32.32 . Cytogenetics and Cell Genetics . 73 . 1–2 . 99–103 . 1996 . 8646895 . 10.1159/000134317 .
• Sokolova IV, Narovlianskiĭ AN, Amchenkova AM, Turpaev KT . [Alternative splicing of 5'-terminal exons of the human tryptophanyl-tRNA synthetase gene] . Molekuliarnaia Biologiia . 30 . 2 . 319–329 . 1996 . 8724762 .
• Krause SW, Rehli M, Kreutz M, Schwarzfischer L, Paulauskis JD, Andreesen R . Differential screening identifies genetic markers of monocyte to macrophage maturation . Journal of Leukocyte Biology . 60 . 4 . 540–545 . October 1996 . 8864140 . 10.1002/jlb.60.4.540 . 24891320 .
• Yuan W, Collado-Hidalgo A, Yufit T, Taylor M, Varga J . Modulation of cellular tryptophan metabolism in human fibroblasts by transforming growth factor-beta: selective inhibition of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA synthetase gene expression . Journal of Cellular Physiology . 177 . 1 . 174–186 . October 1998 . 9731757 . 10.1002/(SICI)1097-4652(199810)177:1<174::AID-JCP18>3.0.CO;2-D . 20056701 .
• Jensen LL, Nielsen MM, Justesen J, Hansen LL . Assignment of human NADH dehydrogenase (ubiquinone) 1 beta subcomplex 3 (NDUFB3) and of its four pseudogenes to human chromosomes 2q31.3, 1p13.3-->p13.1, 9q32-->q34.1, 14q22.3-->q23.1 and 14q32.2 by radiation hybrid mapping . Cytogenetics and Cell Genetics . 93 . 1–2 . 147–150 . 2001 . 11474204 . 10.1159/000056973 . 2435568 .
• Otani A, Slike BM, Dorrell MI, Hood J, Kinder K, Ewalt KL, Cheresh D, Schimmel P, Friedlander M . 6 . A fragment of human TrpRS as a potent antagonist of ocular angiogenesis . Proceedings of the National Academy of Sciences of the United States of America . 99 . 1 . 178–183 . January 2002 . 11773625 . 117535 . 10.1073/pnas.012601899 . 2002PNAS...99..178O . free .
• Wakasugi K, Slike BM, Hood J, Otani A, Ewalt KL, Friedlander M, Cheresh DA, Schimmel P . 6 . A human aminoacyl-tRNA synthetase as a regulator of angiogenesis . Proceedings of the National Academy of Sciences of the United States of America . 99 . 1 . 173–177 . January 2002 . 11773626 . 117534 . 10.1073/pnas.012602099 . 2002PNAS...99..173W . free .
• Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S . Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex . Biochemical and Biophysical Research Communications . 291 . 1 . 158–164 . February 2002 . 11829477 . 10.1006/bbrc.2002.6398 .
• Guo Q, Gong Q, Tong KL, Vestergaard B, Costa A, Desgres J, Wong M, Grosjean H, Zhu G, Wong JT, Xue H . 6 . Recognition by tryptophanyl-tRNA synthetases of discriminator base on tRNATrp from three biological domains . The Journal of Biological Chemistry . 277 . 16 . 14343–14349 . April 2002 . 11834741 . 10.1074/jbc.M111745200 . free .

Notes and References

1. Buwitt U, Flohr T, Böttger EC . Molecular cloning and characterization of an interferon induced human cDNA with sequence homology to a mammalian peptide chain release factor . The EMBO Journal . 11 . 2 . 489–496 . February 1992 . 1537332 . 556479 . 10.1002/j.1460-2075.1992.tb05079.x .
2. Fleckner J, Rasmussen HH, Justesen J . Human interferon gamma potently induces the synthesis of a 55-kDa protein (gamma 2) highly homologous to rabbit peptide chain release factor and bovine tryptophanyl-tRNA synthetase . Proceedings of the National Academy of Sciences of the United States of America . 88 . 24 . 11520–11524 . December 1991 . 1763065 . 53167 . 10.1073/pnas.88.24.11520 . 1991PNAS...8811520F . free .
3. Web site: Entrez Gene: WARS tryptophanyl-tRNA synthetase.
4. Pataskar A, Champagne J, Nagel R, Kenski J, Laos M, Michaux J, Pak HS, Bleijerveld OB, Mordente K, Navarro JM, Blommaert N, Nielsen MM, Lovecchio D, Stone E, Georgiou G, de Gooijer MC, van Tellingen O, Altelaar M, Joosten RP, Perrakis A, Olweus J, Bassani-Sternberg M, Peeper DS, Agami R . 6 . Tryptophan depletion results in tryptophan-to-phenylalanine substitutants . Nature . 721–727 . March 2022 . 603 . 7902 . 35264796 . 10.1038/s41586-022-04499-2 . 8942854 . 2022Natur.603..721P .