Biopolym. Cell. 2013; 29(3):177-187.
Обзоры
Особенности биосинтеза белка у высших эукариотов
1Ельская А. В., 1Негруцкий Б. С., 1Шалак В. Ф., 1Висловух А. А., 1Власенко Д. О., 1Новосильная А. В., 1Лукаш Т. А., 1Веремьева М. В.
  1. Институт молекулярной биологии и генетики НАН Украины
    ул. Академика Заболотного, 150, Киев, Украина, 03680

Abstract

В обзоре суммированы наиболее значимые результаты более чем сорокалетнего исследования особенностей трансляции у высших эукариот, среди них: 1) открытие адаптации клеточных пулов тРНК и аминоацил-тРНК синтетаз (АРСаз) к синтезу специфических белков и модуляции скорости элонгации редкими изоакцепторными тРНК; 2) определение шапероноподобных свойств компонентов аппарата трансляции (рибосом и фактора элонгации eEF1A) и характеристика высокомолекулярных комплексов АРСаз; 3) установление функциональной компартментализации, включающей каналирование тРНК в эукариотных клетках; 4) выяснение молекулярных механизмов каналирования, опосредованного неканоническими комплексами, содержащими eEF1A, тРНК и АРС-азы; 5) характеристика кристаллической структуры eEF1A2; 6) сравнение пространственной организации, молекулярной динамики, тирозинового фосфорилирования и способности к взаимодействию с различными белками – партнерами изоформ eEF1A1 и eEF1A2; 7) выявление роли микроРНК в контроле экспрессии протоонкогенной изоформы eEF1A2 в раковых клетках; 8) изучение связанных с раком изменений комплекса факторов элонгации трансляции eEF1H и механизмов действия онкогена РТІ-1; 9) открытие третьего сайта связывания тРНК в рибосомах млекопитающих и аллостерического взаимодействия А- и Е-сайтов на 80S рибосомах.
Keywords: биосинтез белка, тРНК, аминоацил-тРНК синтетазы, eEF1A, eEF1H, РТІ-1

References

[1] El'skaya A. V., Matsuka G. Kh. Contribution to the alteration in the set of individual tRNA in the mammary gland cells depending upon quality of synthesized protein Ukr. Biokhim. Zh. 1968 40, N 2:120–124.
[2] Matsuka G. Kh., El'skaya A. V., Kovalenko M. I., Korneluk A. I. Transport ribonucleic acids Kiev: Nauk. dumka, 1976 219 p.
[3] El'skaya A. V., Matsuka G., Matiash U., Nazarenko I., Semenova N. tRNA and aminoacyl-tRNA synthetases during differentiation and various functional states of Mammary Gland Biochim. Biophys. Acta 1971 247, N 2:430–440.
[4] El'skaya A. V. Adapter-modification hypothesis of the regulatory function of tRNA Mol. Biol 1971 7, N 13:152–165.
[5] El'skaya A. V., Starodub N. F., Potapov A. P., Kovalenko M. I., Ovcharenko G. V., Obolenskaya M. U., Ivanov L. L. Regulation of protein biosynthesis in eukaryotes Kiev: Nauk. dumka, 1990 280 p.
[6] Elskaya AV, Turkovskaya GV, Rachkov AE, Starodub NF. The role of tRNA in regulation of specific protein biosynthesis. Doklady Akad Nauk Ukr SSR. Ser B. 1982; (7):64–7.
[7] El'skaya A. V. Regulation of protein synthesis in higher eukaryotes: Facts and hypotheses Mol. Biol (Mosk) 1999 33, N 6:1043–1053.
[8] Gudzera O. I., El'skaya A. V., Ovcharenko G. V., Ivanov L. L., Baturina I. D., Matsuka G. Kh. Purufication and properties of Leucyl-tRNA synthetase from the cow mammary gland Mol. Biol (Mosk) 1979 13, N 3:550–557.
[9] Gudzera O. I., El'skaya A. V., Ovcharenko G. V., Kovalenko M. I., Matsuka G. Kh. Study of the aminoacyl-tRNA-synthetases upon mammary gland differentiation Mol. Biol 1978 20, N 10:12–22.
[10] Yaremchuk A. D., El'skaya A. V. Biological activity of tRNA, aminoacyl-tRNA-synthetases and composition of their high-molecular complexes in the rat regenerating liver Ukr. Biochim. Zh. 1983 55, N 4:363–367.
[11] Duran R. V., Hall M. N. Leucyl-tRNA synthetase: double duty in amino acid sensing Cell Res 2012 22, N 8:1207–1209.
[12] Bandyopadhyay AK, Deutscher MP. Complex of aminoacyl-transfer RNA synthetases. J Mol Biol. 1971;60(1):113-22.
[13] Ivanov L. L., Yaremchuk A. D., Stapulyenis R. R., Tamulyavichus A. I., Buldakova O. V., Kovalenko M. I., El'skaya A. V. Study of high-molecular organization of eukaryotic aminoacyltRNA synthetases Ukr biokhim Zh. 1986 58, N 6:368–371.
[14] Rodovitus G. A., Ivanov L. L., Lukoshevichius L. I, Kovalenko M. I., El’skaya A. V. Aminoacyl-tRNA synthetases of the rat liver under experimental myocardial infarction. Doklady Akad Nauk Ukr SSR. Ser B. 1982 4, N 2 P. 63–65.
[15] Yaremchuk AD, Goncharov NI, Bogdanaite OD, Kondratyuk TP, Tarasevichene LV, El'skaya AV. Aminoacyl-tRNA synthetases complexes under sharp changes in protein biosynthesis. Doklady Akad Nauk Ukr SSR. Ser B. 1984 3(3):82–5.
[16] Yaremchuk A. D., Tarasevichene L. E., Kondratjuk T. P., El'skaya A. V. Aminoacyl-tRNA synthetases and their high-molecular complexes from rat regenerating liver Mol Biol (Mosk) 1984 18, N 5:1336–1341.
[17] Lzhanova A. T., Fedorov A. N., Ovchinnikov L. P. AminoacyltRNA synthetases of rabbit reticulocytes with and without the ability to bind high-Mr RNA FEBS Lett 1982 144, N 4:149–153.
[18] Ivanov L. L., Martinkus Z., Kharchenko O. V., Sana S., Lukoshevichius L., Prashkevichius A., El'skaya A. V. Subcellular distribution and properties of rabbit liver aminoacyl-tRNA synthetases under myocardial ischemia Mol. Cell. Biochem 1993 125, N 9:105–114.
[19] Kaminska M., Havrylenko S., Decottignies P., Le Marechal P., Negrutskii B., Mirande M. Dynamic organization of aminoacyltRNA synthetase complexes in the cytoplasm of human cells J. Biol. Chem 2009 284, N 20:13746–13754.
[20] Havrylenko S., Legouis R., Negrutskii B., Mirande M. Caenorhabditis elegans evolves a new architecture for the multi-aminoacyl-tRNA synthetase complex J. Biol. Chem 2011 286, N 32:28476–28487.
[21] Negrutskii B. S., Deutscher M. P. Channeling of aminoacyl-tRNA for protein synthesis in vivo Proc. Natl Acad. Sci. USA 1991 88, N 11:4991–4995.
[22] Negrutskii B. S., Stapulionis R., Deutscher M. P. Supramolecular organization of the mammalian translation system Proc. Natl Acad. Sci. USA 1994 91, N 3:964–968.
[23] Negrutskii B. S., Budkevich T. V., Shalak V. F., Turkovskaya G. V., El'skaya A. V. Rabbit translation elongation factor 1 alpha stimulates the activity of homologous aminoacyl-tRNA synthetase FEBS Lett 1996 382, N 1–2:18–20.
[24] Lukash T. O., Turkivska H. V., Negrutskii B. S., El'skaya A. V. Chaperone-like activity of mammalian elongation factor eEF1A: renaturation of aminoacyl-tRNA synthetases Int. J. Biochem. Cell Biol 2004 36, N 7:1341–1347.
[25] Petrushenko Z. M., Negrutskii B. S., Ladokhin A. S., Budkevich T. V., Shalak V. F., El'skaya A. V. Evidence for the formation of an unusual ternary complex of rabbit liver EF-1alpha with GDP and deacylated tRNA FEBS Lett 1997 407, N 1:13–17.
[26] Negrutskii B. S., Shalak V. F., Kerjan P., El'skaya A. V., Mirande M. Functional interaction of mammalian valyl-tRNA synthetase with elongation factor EF-1alpha in the complex with EF1H J. Biol. Chem 1999 274, N 8:4545–4550.
[27] Petrushenko Z. M., Budkevich T. V., Shalak V. F., Negrutskii B. S., El'skaya A. V. Novel complexes of mammalian translation elongation factor eEF1A.GDP with uncharged tRNA and aminoacyl-tRNA synthetase. Implications for tRNA channeling Eur. J. Biochem 2002 269, N 19:4811–4818.
[28] Negrutskii B. S., El'skaya A. V. Eukaryotic translation elongation factor 1 alpha: structure, expression, functions, and possible role in aminoacyl-tRNA channeling Prog. Nucleic Acid Res. Mol. Biol 1998 60:47–78.
[29] Negrutskii B. S., El'skaia A. V. Functional compartmentation of the translation apparatus and channeling of tRNA/aminoacyltRNA in cells of higher eukaryotes Mol. Biol 2001 35, N 4 P. 702–707.
[30] Andersen G. R., Pedersen L., Valente L., Chatterjee I., Kinzy T. G., Kjeldgaard M., Nyborg J. Structural basis for nucleotide exchange and competition with tRNA in the yeast elongation factor complex eEF1A:eEF1Balpha Mol. Cell 2000 6, N 5 P. 1261–1266.
[31] Yaremchuk A., Shalak V. F., Novosylna O. V., Negrutskii B. S., Crepin T., El'skaya A. V., Tukalo M. Purification, crystallization and preliminary X-ray crystallographic analysis of mammalian translation elongation factor eEF1A2 Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun 2012 68, Pt 3:295–297.
[32] Budkevich T. V., Timchenko A. A., Tiktopulo E. I., Negrutskii B. S., Shalak V. F., Petrushenko Z. M., Aksenov V. L., Willumeit R., Kohlbrecher J., Serdyuk I. N., El'skaya A. V. Extended conformation of mammalian translation elongation factor 1A in solution Biochemistry 2002 41, N 51:15342–15349.
[33] Newbery H. J., Loh D. H., O'Donoghue J. E., Tomlinson V. A., Chau Y. Y., Boyd J. A., Bergmann J. H., Brownstein D., Abbott C. M. Translation elongation factor eEF1A2 is essential for post-weaning survival in mice J. Biol. Chem 2007 282, N 39:28951–28959.
[34] Duttaroy A., Bourbeau D., Wang X. L., Wang E. Apoptosis rate can be accelerated or decelerated by overexpression or reduction of the level of elongation factor-1 alpha Exp. Cell. Res 1998 238, N 1:168–176.
[35] Cao H., Zhu Q., Huang J., Li B., Zhang S., Yao W., Zhang Y. Regulation and functional role of eEF1A2 in pancreatic carcinoma Biochem. Biophys. Res. Commun 2009 380, N 1:11–16.
[36] Pinke D. E., Kalloger S. E., Francetic T., Huntsman D. G., Lee J. M. The prognostic significance of elongation factor eEF1A2 in ovarian cancer Gynecol. Oncol 2008 108, N 3:561–568.
[37] Scaggiante B., Dapas B., Bonin S., Grassi M., Zennaro C., Farra R., Cristiano L., Siracusano S., Zanconati F., Giansante C., Grassi G. Dissecting the expression of EEF1A1/2 genes in human prostate cancer cells: the potential of EEF1A2 as a hallmark for prostate transformation and progression Br. J. Cancer 2012 106, N 1:166–173.
[38] Lee J. M. The role of protein elongation factor eEF1A2 in ovarian cancer Reprod. Biol. Endocrinol 2003 1:69.
[39] Anand N., Murthy S., Amann G., Wernick M., Porter L. A., Cukier I. H., Collins C., Gray J. W., Diebold J., Demetrick D. J., Lee J. M. Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer Nat. Genet 2002 31, N 3:301–305.
[40] Tomlinson V. A., Newbery H. J., Wray N. R., Jackson J., Larionov A., Miller W. R., Dixon J. M., Abbott C. M. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours BMC cancer 2005 5:113.
[41] Zhu H., Lam D. C., Han K. C., Tin V. P., Suen W. S., Wang E., Lam W. K., Cai W. W., Chung L. P., Wong M. P. High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines Cancer Lett 2007 245, N 1–2:303–314.
[42] Kanibolotsky D. S., Novosyl'na O. V., Abbott C. M., Negrutskii B. S. Multiple molecular dynamics simulation of the isoforms of human translation elongation factor 1A reveals reversible fluctuations between «open» and «closed» conformations and suggests specific for eEF1A1 affinity for Ca2+-calmodulin BMC Struct. Biol 2008 8:4.
[43] Panasyuk G., Nemazanyy I., Filonenko V., Negrutskii B., El'skaya A. V. A2 isoform of mammalian translation factor eEF1A displays increased tyrosine phosphorylation and ability to interact with different signalling molecules Int. J. Biochem. Cell Biol 2008 40, N 1:63–71.
[44] Negrutskii B., Vlasenko D., El'skaya A. From global phosphoproteomics to individual proteins: the case of translation elongation factor eEF1A Expert Rev. Proteomics 2012 9, N 1 P. 71–83.
[45] Mayya V., Han D. K. Phosphoproteomics by mass spectrometry: insights, implications, applications and limitations Expert Rev. Proteomics 2009 6, N 6:605–618.
[46] Timchenko A., Serdyuk I., Negrutskii B., Novosylna A., Prituzhalov E., Kimura K., Kihara H. Study of complex formation between calmodulin and two isoforms of rabbit elongation factor eEF1-A by SAXS method Photon Factory Activity Report 2008 25, part B:247.
[47] Novosylna A. V., Timchenko A. A., Tiktopulo E. I., Serdyuk I. N., Negrutskii B. S., El'skaya A. V. Characterization of physical properties of two isoforms of translation elongation factor 1A Biopolym. Cell 2007 23, N 5:386–390.
[48] Tomlinson V. A., Newbery H. J., Bergmann J. H., Boyd J., Scott D., Wray N. R., Sellar G. C., Gabra H., Graham A., Williams A. R., Abbott C. M. Expression of eEF1A2 is associated with clear cell histology in ovarian carcinomas: overexpression of the gene is not dependent on modifications at the EEF1A2 locus Br. J. Cancer 2007 96, N 10:1613–1620.
[49] Vislovukh A. A., Naumovets M. G., Kovalenko M. I., Groisman R. S., Groisman I. S., Negrutskii B. S., El'skaya A. V. Isoforms of elongation factor eEF1A may be differently regulated at posttranscriptional level in breast cancer progression Biopolym. Cell 2013 29, N 1:55–63.
[50] Vislovukh A. A., Groisman I. S., El'skaya A. V., Negrutskii B. S., Polesskaya A. N. Transcriptional and post-transcriptional control of eEF1A2 expression during myoblast diffrerentiation Biopolym. Cell 2012 28, N 6:456–460.
[51] Pogribna A. P., Negrutskii B. S., El'skaya A. V. Removal of part of the eEF1A GTP binding domain induced translation errors in vitro Biopolym. Cell 2006 22, N 3:186–191.
[52] Mansilla F., Hansen L. L., Jakobsen H., Kjeldgaard N. O., Clark B. F., Knudsen C. R. Deconstructing PTI-1: PTI-1 is a truncated, but not mutated, form of translation elongatin factor 1A1, eEF1A1 Biochim. Biophys. Acta 2005 1727, N 2:116–124.
[53] Vislovukh A. A., Shalak V. F., Savytskyi O. V., Kovalenko N. I., Gralievska N. L., Negrutskii B. S., El'skaya A. V. PTI-1: novel way to oncogenicity Biopolym. Cell 2012 28, N 5:404–410.
[54] Veremieva M., Khoruzhenko A., Zaicev S., Negrutskii B., El'skaya A. Unbalanced expression of the translation complex eEF1 subunits in human cardioesophageal carcinoma Eur. J. Clin. Invest 2011 41, N 3:269–276.
[55] Rodnina M. V., El'skaya A. V., Semenkov Yu. P., Kirillov S. V. Number of tRNA binding sites on 80S ribosomes and their subunits FEBS Lett 1988 231, N 1:71–74.
[56] Rodnina M. V., El'skaya A. V., Semenkov Y. P., Kirillov S. V. Interaction of tRNA with the A and P sites of rabbit-liver 80S ribosomes and their 40S subunits Eur. J. Biochem 1989 185, N 3:563–568.
[57] Rodnina M. V., Serebryanik A. I., Ovcharenko G. V., El'skaya A. V. ATPase strongly bound to higher eukaryotic ribosomes Eur. J. Biochem 1994 225, N 1:305–310.
[58] El'skaya A. V., Ovcharenko G. V., Palchevskii S. S., Petrushenko Z. M., Triana-Alonso F. J., Nierhaus K. H. Three tRNA binding sites in rabbit liver ribosomes and role of the intrinsic ATPase in 80S ribosomes from higher eukaryotes Biochemistry 1997 36, N 34:10492–10497.
[59] Budkevich T. V., El'skaya A. V., Nierhaus K. H. Features of 80S mammalian ribosome and its subunits Nucleic Acids Res 2008 36, N 14:4736–4744.
[60] Budkevich T., Giesebrecht J., Altman R. B., Munro J. B., Mielke T., Nierhaus K. H., Blanchard S. C., Spahn C. M. Structure and dynamics of the mammalian ribosomal pretranslocation complex Mol. Cell 2011 44, N 2:214–224.