The co-translational incorporation of selenocysteine (Sec) requires that UGA be recognized as a sense rather than a nonsense codon. This is accomplished by the concerted action of a Sec insertion sequence (SECIS) element, SECIS binding protein 2, and a ternary complex of the Sec specific elongation factor, Sec-tRNASec, and GTP. The mechanism by which they alter the canonical protein synthesis reaction has been elusive. Here we present an overview of the mechanistic perspective on Sec incorporation, highlighting recent advances in the field. Antioxid. Redox Signal. 12, 881–892.
Get full access to this article
View all access options for this article.
References
1.
AllmangC, CarbonP, KrolA. The SBP2 and 15.5 kD/Snu13p proteins share the same RNA binding domain: identification of SBP2 amino acids important to SECIS RNA binding. RNA, 8:1308–1318. 2002.
2.
AlsinaB, CorominasM, BerryMJ, BaguñaJ, SerrasF. Disruption of selenoprotein biosynthesis affects cell proliferation in the imaginal discs and brain of Drosophila melanogaster. J Cell Sci, 112:2875–2884. 1999.
3.
AndersenGR, PedersenL, ValenteL, ChatterjeeI, KinzyTG, KjeldgaardM, NyborgJ. Structural basis for nucleotide exchange and competition with tRNA in the yeast elongation factor complex eEF1A:eEF1Balpha. Mol Cell, 6:1261–1266. 2000.
4.
BaronC, HeiderJ, BöckA. Interaction of translation factor SELB with the formate dehydrogenase H selenopolypeptide mRNA. Proc Natl Acad Sci USA, 90:4181–4185. 1993.
5.
BoulonS, Marmier–GourrierN, Pradet–BaladeB, WurthL, VerheggenC, JádyBE, RothéB, PesciaC, RobertMC, KissT, BardoniB, KrolA, BranlantC, AllmangC, BertrandE, CharpentierB. The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery. J Cell Biol, 180:579–595. 2008.
6.
BöslMR, TakakuK, OshimaM, NishimuraS, TaketoMM. Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene (Trsp)Proc Natl Acad Sci USA, 94:5531–5534. 1997.
7.
BubenikJL, DriscollDM. Altered RNA binding activity underlies abnormal thyroid hormone metabolism linked to a mutation in selenocysteine insertion sequence-binding protein 2. J Biol Chem, 282:34653–34662. 2007.
8.
CabanK, CopelandPR. Size matters: A view of selenocysteine incorporation from the ribosome. Cell Mol Life Sci, 63:73–81. 2006.
9.
CabanK, KinzySA, CopelandPR. The L7Ae RNA binding motif is a multifunctional domain required for the ribosome-dependent Sec incorporation activity of Sec insertion sequence binding protein 2. Mol Cell Biol, 27:6350–6360. 2007.
10.
ChappleCE, GuigóR. Relaxation of selective constraints causes independent selenoprotein extinction in insect genomes. PLoS ONE, 3:e2968. 2008.
11.
ChappleCE, GuigóR, KrolA. SECISaln, a web-based tool for the creation of structure-based alignments of eukaryotic SECIS elements. Bioinformatics, 25:674–675. 2009.
12.
ChavatteL, BrownBA, DriscollDM. Ribosomal protein L30 is a component of the UGA-selenocysteine recoding machinery in eukaryotes. Nat Struct Mol Biol, 12:408–416. 2005.
13.
ChristensenMJ, BurgenerKW. Dietary selenium stabilizes glutathione peroxidase mRNA in rat liver. J Nutr, 122:1620–1626. 1992.
14.
CopelandPR. Regulation of gene expression by stop codon recoding: selenocysteine. Gene, 312:17–25. 2003.
15.
CopelandPR, DriscollDM. Purification, redox sensitivity, and RNA binding properties of SECIS-binding protein 2, a protein involved in selenoprotein biosynthesis. J Biol Chem, 274:25447–25454. 1999.
16.
CopelandPR, FletcherJE, CarlsonBA, HatfieldDL, DriscollDM. A novel RNA binding protein, SBP2, is required for the translation of mammalian selenoprotein mRNAs. EMBO J, 19:306–314. 2000.
17.
CopelandPR, StepanikVA, DriscollDM. Insight into mammalian selenocysteine insertion: Domain structure and ribosome binding properties of Sec insertion sequence binding protein 2. Mol Cell Biol, 21:1491–1498. 2001.
18.
DonovanJ, CabanK, RanaweeraR, Gonzales–FloresJN, CopelandPR. A novel protein domain induces high affinity selenocysteine insertion sequence binding and elongation factor recruitment. J Biol Chem, 283:35129–35139. 2008.
19.
DonovanJ, CopelandPR. Evolutionary history of selenocysteine incorporation from the perspective of SECIS binding proteins. BMC Evol Biol, Sep10, 2009[Epub]
20.
FagegaltierD, HubertN, YamadaK, MizutaniT, CarbonP, KrolA. Characterization of mSelB, a novel mammalian elongation factor for selenoprotein translation. EMBO J, 19:4796–4805. 2000.
21.
FletcherJE, CopelandPR, DriscollDM, KrolA. The selenocysteine incorporation machinery: interactions between the SECIS RNA and the SECIS-binding protein SBP2. RNA, 7:1442–1453. 2001.
22.
FourmyD, GuittetE, YoshizawaS. Structure of prokaryotic SECIS mRNA hairpin and its interaction with elongation factor SelB. J Mol Biol, 324:137–150. 2002.
23.
Grundner–CulemannE, MartinGW, HarneyJW, BerryMJ. Two distinct SECIS structures capable of directing selenocysteine incorporation in eukaryotes. RNA, 5:625–635. 1999.
24.
GuimarãesMJ, PetersonD, VicariA, CocksBG, CopelandNG, GilbertDJ, JenkinsNA, FerrickDA, KasteleinRA, BazanJF, ZlotnikA. Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: Is there an autoregulatory mechanism in selenocysteine metabolism?Proc Natl Acad Sci USA, 93:15086–15091. 1996.
25.
GuptaM, CopelandPR. Functional analysis of the interplay between translation termination, selenocysteine codon context, and selenocysteine insertion sequence-binding protein 2. J Biol Chem, 282:36797–36807. 2007.
26.
HenrasAK, DezC, HenryY. RNA structure and function in C/D and H/ACA s (no) RNPs. Curr Opin Struct Biol, 14:335–343. 2004.
27.
HillKE, LloydRS, BurkRF. Conserved nucleotide sequences in the open reading frame and 3' untranslated region of selenoprotein P mRNA. Proc Natl Acad Sci USA, 90:537–541. 1993.
28.
HillKE, ZhouJ, AustinLM, MotleyAK, HamAJL, OlsonGE, AtkinsJF, GestelandRF, BurkRF. The selenium-rich C-terminal domain of mouse selenoprotein P is necessary for the supply of selenium to brain and testis but not for the maintenance of whole body selenium. J Biol Chem, 282:10972–10980. 2007.
29.
Hirosawa–TakamoriM, ChungHR, JäckleH. Conserved selenoprotein synthesis is not critical for oxidative stress defence and the lifespan of Drosophila. EMBO Rep, 5:317–322. 2004.
30.
Hirosawa–TakamoriM, JäckleH, VorbrüggenG. The class 2 selenophosphate synthetase gene of Drosophila contains a functional mammalian-type SECIS. EMBO Rep, 1:441–446. 2000.
31.
HowardMT, AggarwalG, AndersonCB, KhatriS, FlaniganKM, AtkinsJF. Recoding elements located adjacent to a subset of eukaryal selenocysteine-specifying UGA codons. EMBO J, 24:1596–1607. 2005.
32.
HowardMT, MoyleMW, AggarwalG, CarlsonBA, AndersonCB. A recoding element that stimulates decoding of UGA codons by Sec tRNA[Ser]Sec. RNA, 13:912–920. 2007.
33.
HüttenhoferA, BöckA. Selenocysteine inserting RNA elements modulate GTP hydrolysis of elongation factor SelB. Biochemistry, 37:885–890. 1998.
34.
de JesusLA, HoffmannPR, MichaudT, ForryEP, Small–HowardA, StillwellRJ, MorozovaN, HarneyJW, BerryMJ. Nuclear assembly of UGA decoding complexes on selenoprotein mRNAs: A mechanism for eluding nonsense-mediated decay?Mol Cell Biol, 26:1795–1805. 2006.
35.
KinzySA, CabanK, CopelandPR. Characterization of the SECIS binding protein 2 complex required for the co-translational insertion of selenocysteine in mammals. Nucleic Acids Res, 33:5172–5180. 2005.
36.
KleinDJ, SchmeingTM, MoorePB, SteitzTA. The kink-turn: A new RNA secondary structure motif. EMBO J, 20:4214–4221. 2001.
37.
KooninEV, BorkP, SanderC. A novel RNA-binding motif in omnipotent suppressors of translation termination, ribosomal proteins and a ribosome modification enzyme?Nucleic Acids Res, 22:2166–2167. 1994.
38.
KorotkovKV, NovoselovSV, HatfieldDL, GladyshevVN. Mammalian selenoprotein in which selenocysteine (Sec) incorporation is supported by a new form of Sec insertion sequence element. Mol Cell Biol, 22:1402–1411. 2002.
LeibundgutM, FrickC, ThanbichlerM, BöckA, BanN. Selenocysteine tRNA-specific elongation factor SelB is a structural chimaera of elongation and initiation factors. EMBO J, 24:11–22. 2005.
41.
LescureA, AllmangC, YamadaK, CarbonP, KrolA. cDNA cloning, expression pattern and RNA binding analysis of human selenocysteine insertion sequence (SECIS) binding protein 2. Gene, 291:279–285. 2002.
42.
LesoonA, MehtaA, SinghR, ChisolmGM, DriscollDM. An RNA-binding protein recognizes a mammalian selenocysteine insertion sequence element required for cotranslational incorporation of selenocysteine. Mol Cell Biol, 17:1977–1985. 1997.
43.
LobanovAV, HatfieldDL, GladyshevVN. Selenoproteinless animals: Selenophosphate synthetase SPS1 functions in a pathway unrelated to selenocysteine biosynthesis. Protein Sci, 17:176–182. 2008.
MixH, LobanovAV, GladyshevVN. SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes. Nucleic Acids Res, 35:414–423. 2007.
50.
MoonSJ, KöttgenM, JiaoY, XuH, MontellC. A taste receptor required for the caffeine response in vivo. Curr Biol, 16:1812–1817. 2006.
51.
MoriartyPM, ReddyCC, MaquatLE. The presence of an intron within the rat gene for selenium-dependent glutathione peroxidase 1 is not required to protect nuclear RNA from UGA-mediated decay. RNA, 3:1369–1373. 1997.
52.
MoriartyPM, ReddyCC, MaquatLE. Selenium deficiency reduces the abundance of mRNA for Se-dependent glutathione peroxidase 1 by a UGA-dependent mechanism likely to be nonsense codon-mediated decay of cytoplasmic mRNA. Mol Cell Biol, 18:2932–2939. 1998.
53.
NobleCG, SongH. Structural studies of elongation and release factors. Cell Mol Life Sci, 65:1335–1346. 2008.
54.
NovoselovSV, KryukovGV, XuXM, CarlsonBA, HatfieldDL, GladyshevVN. Selenoprotein H is a nucleolar thioredoxin-like protein with a unique expression pattern. J Biol Chem, 282:11960–11968. 2007.
55.
NovoselovSV, LobanovAV, HuaD, KasaikinaMV, HatfieldDL, GladyshevVN. A highly efficient form of the selenocysteine insertion sequence element in protozoan parasites and its use in mammalian cells. Proc Natl Acad Sci USA, 104:7857–7862. 2007.
56.
NovoselovSV, RaoM, OnoshkoNV, ZhiH, KryukovGV, XiangY, WeeksDP, HatfieldDL, GladyshevVN. Selenoproteins and selenocysteine insertion system in the model plant cell system, Chlamydomonas reinhardtii. EMBO J, 21:3681–3693. 2002.
57.
OttavianoFG, TangSS, HandyDE, LoscalzoJ. Regulation of the extracellular antioxidant selenoprotein plasma glutathione peroxidase (GPx-3) in mammalian cells. Mol Cell Biochem, 327:111–126. 2009.
58.
PappLV, LuJ, StriebelF, KennedyD, HolmgrenA, KhannaKK. The redox state of SECIS binding protein 2 controls its localization and selenocysteine incorporation function. Mol Cell Biol, 26:4895–4910. 2006.
RamosA, LaneAN, HollingworthD, FanTW. Secondary structure and stability of the selenocysteine insertion sequences (SECIS) for human thioredoxin reductase and glutathione peroxidase. Nucleic Acids Res, 32:1746–1755. 2004.
62.
RotherM, ReschA, GardnerWL, WhitmanWB, BöckA. Heterologous expression of archaeal selenoprotein genes directed by the SECIS element located in the 3' non-translated region. Mol Microbiol, 40:900–908. 2001.
63.
SilvaAL, RomãoL. The mammalian nonsense-mediated mRNA decay pathway: To decay or not to decay! Which players make the decision?FEBS Lett, 583:499–505. 2009.
SquiresJE, StoytchevI, ForryEP, BerryMJ. SBP2 binding affinity is a major determinant in differential selenoprotein mRNA translation and sensitivity to nonsense-mediated decay. Mol Cell Biol, 27:7848–7855. 2007.
66.
StockT, RotherM. Selenoproteins in Archaea and Gram-positive bacteria. Biochim Biophys Acta, 1790:1520–1532. 2009.
67.
StoytchevaZ, TujebajevaRM, HarneyJW, BerryMJ. Efficient incorporation of multiple selenocysteines involves an inefficient decoding step serving as a potential translational checkpoint and ribosome bottleneck. Mol Cell Biol, 26:9177–9184. 2006.
68.
SuD, HohnMJ, PaliouraS, SherrerRL, YuanJ, SöllD, O'DonoghueP. How an obscure archaeal gene inspired the discovery of selenocysteine biosynthesis in humans. IUBMB Life, 61:35–39. 2009.
69.
SunQA, KirnarskyL, ShermanS, GladyshevVN. Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. Proc Natl Acad Sci USA, 98:3673–3678. 2001.
70.
SuppmannS, PerssonBC, BöckA. Dynamics and efficiency in vivo of UGA-directed selenocysteine insertion at the ribosome. EMBO J, 18:2284–2293. 1999.
71.
TakeuchiA, SchmittD, ChappleC, BabaylovaE, KarpovaG, GuigoR, KrolA, AllmangC. A short motif in Drosophila SECIS Binding Protein 2 provides differential binding affinity to SECIS RNA hairpins. Nucleic Acids Res, 37:2126–2141. 2009.
TujebajevaRM, RansomDG, HarneyJW, BerryMJ. Expression and characterization of nonmammalian selenoprotein P in the zebrafish, Danio rerio. Genes Cells, 5:897–903. 2000.
75.
TuranovAA, LobanovAV, FomenkoDE, MorrisonHG, SoginML, KlobutcherLA, HatfieldDL, GladyshevVN. Genetic code supports targeted insertion of two amino acids by one codon. Science, 323:259–261. 2009.
76.
UferC, WangCC, FählingM, SchiebelH, ThieleBJ, BillettEE, KuhnH, BorchertA. Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development. Genes Dev, 22:1838–1850. 2008.
77.
WalczakR, CarbonP, KrolA. An essential non-Watson-Crick base pair motif in 3'UTR to mediate selenoprotein translation. RNA, 4:74–84. 1998.
78.
WalczakR, WesthofE, CarbonP, KrolA. A novel RNA structural motif in the selenocysteine insertion element of eukaryotic selenoprotein mRNAs. RNA, 2:367–379. 1996.
79.
WeissSL, SundeRA. Cis-acting elements are required for selenium regulation of glutathione peroxidase-1 mRNA levels. RNA, 4:816–827. 1998.
80.
ZavackiAM, MansellJB, ChungM, KlimovitskyB, HarneyJW, BerryMJ. Coupled tRNA(Sec)-dependent assembly of the selenocysteine decoding apparatus. Mol Cell, 11:773–781. 2003.
