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title TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish
authors Reverendo, M; Soares, AR; Pereira, PM; Carreto, L; Ferreira, V; Gatti, E; Pierre, P; Moura, GR; Santos, MA
author full name Reverendo, Marisa; Soares, Ana R.; Pereira, Patricia M.; Carreto, Laura; Ferreira, Violeta; Gatti, Evelina; Pierre, Philippe; Moura, Gabriela R.; Santos, Manuel A.
title TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish
nationality nacional
source RNA BIOLOGY
language English
document type Article
author keywords tRNA; mRNA mistranslation; proteotoxic stress; protein aggregation; ROS; zebrafish
keywords plus UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; GREEN-FLUORESCENT PROTEIN; ER-ASSOCIATED DEGRADATION; MITOCHONDRIAL-DNA DAMAGE; OXIDATIVE STRESS; MAMMALIAN-CELLS; TRANSLATIONAL REPRESSION; EMBRYONIC-DEVELOPMENT; MODIFICATION DEFECT
abstract Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through proteome instability and saturation of the proteostasis network. To test this hypothesis we have induced mistranslation in zebrafish embryos using mutant tRNAs that misincorporate Serine (Ser) at various non-cognate codon sites. Embryo viability was affected and malformations were observed, but a significant proportion of embryos survived by activating the unfolded protein response (UPR), the ubiquitin proteasome pathway (UPP) and downregulating protein biosynthesis. Accumulation of reactive oxygen species (ROS), mitochondrial and nuclear DNA damage and disruption of the mitochondrial network, were also observed, suggesting that mistranslation had a strong negative impact on protein synthesis rate, ER and mitochondrial homeostasis. We postulate that mistranslation promotes gradual cellular degeneration and disease through protein aggregation, mitochondrial dysfunction and genome instability.
author address [Reverendo, Marisa; Soares, Ana R.; Pereira, Patricia M.; Carreto, Laura; Ferreira, Violeta; Moura, Gabriela R.; Santos, Manuel A.] Univ Aveiro, iBiMED & Hlth Sci, Aveiro, Portugal; [Gatti, Evelina; Pierre, Philippe] Aix Marseille Univ, Ctr Immunol Marseille Luminy, Marseille, France; [Gatti, Evelina; Pierre, Philippe] INSERM, F-13258 Marseille, France; [Gatti, Evelina; Pierre, Philippe] CNRS, Marseille, France
reprint address Santos, MA (reprint author), Univ Aveiro, iBiMED & Hlth Sci, Aveiro, Portugal.
e-mail address msantos@ua.pt
funding agency and grant number Portuguese Foundation for Science and Technology (FCT) [FCT-ANR/IMI-MIC/0041/2012, SFRH/BD/47868/2008]
funding text The authors are most grateful to the Portuguese Foundation for Science and Technology (FCT) for funding our work through project No FCT-ANR/IMI-MIC/0041/2012, SFRH/BD/47868/2008 to M.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
cited references Berleant D, 2009, CELL BIOCHEM BIOPHYS, V55, P107, DOI 10.1007/s12013-009-9060-9; Betts MJ, 2003, AMINO ACID PROPERTIE; Bladen CL, 2005, NUCLEIC ACIDS RES, V33, P3002, DOI 10.1093/nar.gki613; Braun JEA, 1996, J BIOL CHEM, V271, P25989; Bryantsev AL, 2007, BIOCHEM J, V407, P407, DOI 10.1042/BJ20070195; Bykhovskaya Y, 2004, AM J HUM GENET, V74, P1303, DOI 10.1086/421530; CHANCE B, 1979, PHYSIOL REV, V59, P527; Chen B, 2011, CSH PERSPECT BIOL, V3, DOI 10.1101/cshperspect.a004374; Chen HC, 2003, J CELL BIOL, V160, P189, DOI 10.1083/jcb.200211046; Chen HC, 2005, J BIOL CHEM, V280, P26185, DOI 10.1074/jbc.M503062200; Chinnadurai G, 2008, ONCOGENE, V27, pS114, DOI 10.1038/onc.2009.49; Chuang JZ, 2002, J BIOL CHEM, V277, P19831, DOI 10.1074/jbc.M109613200; Cinaroglu A, 2011, HEPATOLOGY, V54, P495, DOI 10.1002/hep.24396; Cline SD, 2012, BBA-GENE REGUL MECH, V1819, P979, DOI 10.1016/j.bbagrm.2012.06.002; CODY CW, 1993, BIOCHEMISTRY-US, V32, P1212, DOI 10.1021/bi00056a003; Csordas G, 2009, BBA-BIOENERGETICS, V1787, P1352, DOI 10.1016/j.bbabio.2009.06.004; Cui H., 2012, J SIGNAL TRANSDUCT, V2012, DOI DOI 10.1155/2012/646354; Cusack S, 1996, EMBO J, V15, P2834; Detmer SA, 2007, NAT REV MOL CELL BIO, V8, P870, DOI 10.1038/nrm2275; Drummond DA, 2009, NAT REV GENET, V10, P715, DOI 10.1038/nrg2662; Fortier S, 2009, BIOCHEMISTRY-US, V48, P5396, DOI 10.1021/bi900253d; Francklyn CS, 2010, FEBS LETT, V584, P366, DOI 10.1016/j.febslet.2009.11.045; Freed EF, 2010, MOL BIOSYST, V6, P481, DOI 10.1039/b919670f; Gandre-Babbe S, 2008, MOL BIOL CELL, V19, P2402, DOI 10.1091/mbc.E07-12-1287; Geslain R, 2010, NUCLEIC ACIDS RES, V38, DOI 10.1093/nar/gkp1083; Gething MJ, 1999, SEMIN CELL DEV BIOL, V10, P465, DOI 10.1006/scdb.1999.0318; Giaime E, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0040501; HAIG D, 1991, J MOL EVOL, V33, P412, DOI 10.1007/BF02103132; Harding HP, 2003, MOL CELL, V11, P619, DOI 10.1016/S1097-2765(03)00105-9; Haynes CM, 2004, MOL CELL, V15, P767, DOI 10.1016/j.molcel.2004.08.025; He CC, 2009, AUTOPHAGY, V5, P520; HENIKOFF S, 1992, P NATL ACAD SCI USA, V89, P10915, DOI 10.1073/pnas.89.22.10915; Hu MC, 2007, BIOCHEM BIOPH RES CO, V359, P778, DOI 10.1016/j.bbrc.2007.05.183; Hunter SE, 2010, METHODS, V51, P444, DOI 10.1016/j.ymeth.2010.01.033; Inohara N, 2000, CELL DEATH DIFFER, V7, P509, DOI 10.1038/sj.cdd.4400679; Kaganovich D, 2008, NATURE, V454, P1088, DOI 10.1038/nature07195; Kawahara A, 2005, P NATL ACAD SCI USA, V102, P361, DOI 10.1073/pnas.0408726102; Kim TY, 2008, BIOCHEM BIOPH RES CO, V369, P741, DOI 10.1016/j.bbrc.2008.02.086; KIMMEL CB, 1995, DEV DYNAM, V203, P253; Koga H, 2011, AGEING RES REV, V10, P205, DOI 10.1016/j.arr.2010.02.001; Lang S, 2011, CHANNELS, V5, P228, DOI 10.4161/chan.5.3.15314; Latour P, 2010, AM J HUM GENET, V86, P77, DOI 10.1016/j.ajhg.2009.12.005; Lee JW, 2006, NATURE, V443, P50, DOI 10.1038/nature05096; Lenhard B, 1999, NUCLEIC ACIDS RES, V27, P721, DOI 10.1093/nar/27.3.721; Li XM, 2004, NUCLEIC ACIDS RES, V32, P867, DOI 10.1093/nar/gkh226; Malhotra JD, 2007, SEMIN CELL DEV BIOL, V18, P716, DOI 10.1016/j.semcdb.2007.09.003; Malhotra JD, 2008, P NATL ACAD SCI USA, V105, P18525, DOI 10.1073/pnas.0809677105; Marzec M, 2012, BBA-MOL CELL RES, V1823, P774, DOI 10.1016/j.bbamcr.2011.10.013; Mei YD, 2010, MOL CELL, V37, P668, DOI 10.1016/j.molcel.2010.01.023; Moreno JA, 2012, NATURE, V485, P507, DOI 10.1038/nature11058; Moura G, 2005, GENOME BIOL, V6, DOI 10.1186/gb-2005-6-3-r28; Oda Y, 2006, J CELL BIOL, V172, P383, DOI 10.1083/jcb.200507057; Ojha J, 2011, MOL CELL BIOL, V31, P3146, DOI 10.1128/MCB.01187-10; Park SG, 2008, P NATL ACAD SCI USA, V105, P11043, DOI 10.1073/pnas.0802862105; Phizicky EM, 2010, GENE DEV, V24, P1832, DOI 10.1101/gad.1956510; Proud CG, 2005, SEMIN CELL DEV BIOL, V16, P3, DOI 10.1016/j.semcdb.2004.11.004; Qiu XB, 2006, CELL MOL LIFE SCI, V63, P2560, DOI 10.1007/s00018-006-6192-6; Raturi A, 2013, BBA-MOL CELL RES, V1833, P213, DOI 10.1016/j.bbamcr.2012.04.013; Reid BG, 1997, BIOCHEMISTRY-US, V36, P6786, DOI 10.1021/bi970281w; Ringvoll J, 2008, CANCER RES, V68, P4142, DOI 10.1158/0008-5472.CAN-08-0796; Rodriguez V, 2007, GENE CHROMOSOME CANC, V46, P694, DOI 10.1002/gcc.20454; Rutkowski DT, 2007, MOL BIOL CELL, V18, P3681, DOI 10.1091/mbc.E07-03-0272; Saeed AI, 2006, METHOD ENZYMOL, V411, P134, DOI 10.1016/S0076-6879(06)11009-5; Santos Janine H, 2002, Methods Mol Biol, V197, P159, DOI 10.1385/1-59259-284-8:159; Saotome M, 2008, P NATL ACAD SCI USA, V105, P20728, DOI 10.1073/pnas.0808953105; Schafer A, 2009, EMBO J, V28, P2874, DOI 10.1038/emboj.2009.231; Schmidt EK, 2009, NAT METHODS, V6, P275, DOI [10.1038/nmeth.1314, 10.1038/NMETH.1314]; Shah P, 2010, PLOS GENET, V6, DOI 10.1371/journal.pgen.1001128; Springer W, 2011, AUTOPHAGY, V7, P266, DOI 10.4161/auto.7.3.14348; Stum M, 2011, MOL CELL NEUROSCI, V46, P432, DOI 10.1016/j.mcn.2010.11.006; Suen DF, 2008, GENE DEV, V22, P1577, DOI 10.1101/gad.1658508; TAYLOR WR, 1986, J THEOR BIOL, V119, P205, DOI 10.1016/S0022-5193(86)80075-3; Thompson DM, 2009, CELL, V138, P215, DOI 10.1016/j.cell.2009.07.001; Tondera D, 2005, J CELL SCI, V118, P3049, DOI 10.1242/jcs.02415; Torres AG, 2014, TRENDS MOL MED, V20, P306, DOI 10.1016/j.molmed.2014.01.008; Van Houten B, 2006, DNA REPAIR, V5, P145, DOI 10.1016/j.dnarep.2005.03.002; Ved R, 2005, J BIOL CHEM, V280, P42655, DOI 10.1074/jbc.M505910200; Wakana Y, 2008, MOL BIOL CELL, V19, P1825, DOI 10.1091/mbc.E07-08-0781; Wang SY, 2012, J CELL BIOL, V197, P857, DOI 10.1083/jcb.201110131; WHITE SH, 1992, J MOL BIOL, V227, P991, DOI 10.1016/0022-2836(92)90515-L; Yamasaki S, 2009, J CELL BIOL, V185, P35, DOI 10.1083/jcb.200811106; Yasukawa T, 2001, EMBO J, V20, P4794, DOI 10.1093/emboj/20.17.4794; Yasukawa T, 2000, J BIOL CHEM, V275, P4251, DOI 10.1074/jbc.275.6.4251; Zhang Y, 2001, J CELL BIOCHEM, V82, P692, DOI 10.1002/jcb.1191; Zheng J, 2012, MITOCHONDRION, V12, P406, DOI 10.1016/j.mito.2012.04.001
cited reference count 85
publisher LANDES BIOSCIENCE
publisher city AUSTIN
publisher address 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
issn 1547-6286
29-character source abbreviation RNA BIOL
iso source abbreviation RNA Biol.
publication date SEP
year published 2014
volume 11
issue 9
beginning page 1199
ending page 1213
digital object identifier (doi) 10.4161/rna.32199
page count 15
web of science category Biochemistry & Molecular Biology
subject category Biochemistry & Molecular Biology
document delivery number AZ8KE
unique article identifier WOS:000348463500012
CESAM authors