The length and the secondary structure of the D-stem of human selenocysteine tRNA are the major identity determinants for serine phosphorylation.

Wu, Xinqi; Groß, H.

doi:10.1002/j.1460-2075.1994.tb06254.x

Cited by 26 publications

(35 citation statements)

References 46 publications

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“…In eukarya, the phosphorylation of Ser-tRNA Sec depends mainly on the larger number of base pairs in the D stem, rather than the long acceptor stem or extra arm (50,51). This suggests that PSTK recognizes the D stem structure as the main discrimination site.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of human selenocysteine tRNA

Itoh

Chiba

Sekine

et al. 2009

Nucleic Acids Research

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Selenocysteine (Sec) is the 21st amino acid in translation. Sec tRNA (tRNASec) has an anticodon complementary to the UGA codon. We solved the crystal structure of human tRNASec. tRNASec has a 9-bp acceptor stem and a 4-bp T stem, in contrast with the 7-bp acceptor stem and the 5-bp T stem in the canonical tRNAs. The acceptor stem is kinked between the U6:U67 and G7:C66 base pairs, leading to a bent acceptor-T stem helix. tRNASec has a 6-bp D stem and a 4-nt D loop. The long D stem includes unique A14:U21 and G15:C20a pairs. The D-loop:T-loop interactions include the base pairs G18:U55 and U16:U59, and a unique base triple, U20:G19:C56. The extra arm comprises of a 6-bp stem and a 4-nt loop. Remarkably, the D stem and the extra arm do not form tertiary interactions in tRNASec. Instead, tRNASec has an open cavity, in place of the tertiary core of a canonical tRNA. The linker residues, A8 and U9, connecting the acceptor and D stems, are not involved in tertiary base pairing. Instead, U9 is stacked on the first base pair of the extra arm. These features might allow tRNASec to be the target of the Sec synthesis/incorporation machineries.

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Section: Discussionmentioning

confidence: 99%

Crystal structure of human selenocysteine tRNA

Itoh

Chiba

Sekine

et al. 2009

Nucleic Acids Research

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“…What, then, is the possible role of PSTK and phosphoseryl-tRNA [Ser]Sec in cellular metabolism? It has been speculated that phosphoseryl-tRNA [Ser]Sec may serve as ''an active storage form'' which can, after its dephosphorylation, be regenerated as seryl-tRNA [Ser]Sec for the biosynthesis of Sec (27). Several lines of evidence argue against this proposal.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of phosphoseryl-tRNA ^[Ser]Sec kinase

Carlson

Kryukov

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

174

187

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In 1970, a kinase activity that phosphorylated a minor species of seryl-tRNA to form phosphoseryl-tRNA was found in rooster liver [Maenpaa, P. H. & Bernfield, M. R. (1970) Proc. Natl. Acad. Sci. USA 67, 688 -695], and a minor seryl-tRNA that decoded the nonsense UGA was detected in bovine liver. The phosphoseryl-tRNA and the minor UGA-decoding seryl-tRNA were subsequently identified as selenocysteine (Sec) tRNA [Ser]Sec , but the kinase activity remained elusive. Herein, by using a comparative genomics approach that searched completely sequenced archaeal genomes for a kinase-like protein with a pattern of occurrence similar to that of components of Sec insertion machinery, we detected a candidate gene for mammalian phosphoseryl-tRNA [ S elenocysteine (Sec) has its own code word, UGA, and its own tRNA, and therefore is viewed as the 21st amino acid in the genetic code (reviewed in refs. 1-4). Although UGA usually codes for the termination of protein synthesis, it also specifies Sec if specific requirements are met. The presence of a stemloop structure downstream of UGA, called a Sec insertion sequence (SECIS) element, is the critical component in selenoprotein mRNAs that dictates UGA to code for Sec (reviewed in ref. 5). In mammals, the SECIS element occurs in the 3Ј untranslated region of selenoprotein mRNAs. A specific elongation factor, EFsec, specifically recognizes selenocysteyltRNA [Ser]Sec (6, 7), and a SECIS element binding protein, SBP2, binds specifically to the SECIS element (8), directing the insertion of Sec into protein in response to UGA.It has been known for several years that the biosynthesis of Sec occurs on its tRNA in both bacteria (9) and mammals (10) after the tRNA is initially aminoacylated with serine by seryl-tRNA synthetase. In Escherichia coli, the pathway for the biosynthesis of Sec has been completely established (reviewed in ref. 1). After the aminoacylation of bacterial tRNA [Ser]Sec with serine, the hydroxyl group is removed from the seryl moiety to yield an aminoacrylyl intermediate, and this step is catalyzed by a pyridoxal phosphate-dependent Sec synthase. The aminoacrylyl intermediate serves as the acceptor for the activated selenium donor, monoselenophosphate, which is synthesized from selenite and ATP in the presence of selenophosphate synthetase (reviewed in ref. 1). Once selenium is donated to the intermediate, the biosynthesis of Sec on tRNA [Ser]Sec is complete.In eukaryotes, however, the biosynthesis of Sec has not been established, but several components have been identified over the years that play a role in this process. For example, in 1970, a minor seryl-tRNA was reported to form phosphoseryl-tRNA by a kinase activity from rooster liver (11), and a minor seryl-tRNA from bovine, rabbit, and chicken livers was reported to specifically decode the nonsense codon UGA (12). Although it was subsequently shown that both the minor seryl-tRNA that formed phosphoseryl-tRNA and the one that decoded UGA were the same tRNA (13), it was not known at the time these components were ...

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“…Another important feature observed in T. brucei tRNA Sec is the long D-loop with seven base pairs, contrasting with the tRNA Ser short D-loop of three to four base pairs. The length and secondary structure of the D-loop, but not its sequence composition, are the major components by which archaea and human PSTKs discriminate between tRNA Sec and tRNA Ser [22]. A mutated human tRNA Sec with a fourbase-pair D-loop showed decreased PSTK phosphorylation when compared with the wild type with a six-base-pair Dloop [22], and recent data demonstrated that identification of tRNA Sec in archaea is dependent on the D-loop structure [23].…”

Section: Specific Characteristics Of Kinetoplas-tid Selenocysteine Bimentioning

confidence: 99%

“…The length and secondary structure of the D-loop, but not its sequence composition, are the major components by which archaea and human PSTKs discriminate between tRNA Sec and tRNA Ser [22]. A mutated human tRNA Sec with a fourbase-pair D-loop showed decreased PSTK phosphorylation when compared with the wild type with a six-base-pair Dloop [22], and recent data demonstrated that identification of tRNA Sec in archaea is dependent on the D-loop structure [23]. Moreover, the Kinetoplastidae tRNA Sec has a 7/5 structure in the acceptor-T C stem, with seven nucleotides in the acceptor stem and five nucleotides in the T C stem, while the human [24] and the archaea [25] tRNA Sec have a 9/4 structure.…”

Section: Specific Characteristics Of Kinetoplas-tid Selenocysteine Bimentioning

confidence: 99%

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

Silva¹,

Silva²,

Thiemann³

2014

CMC

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Selenium (Se) is an essential trace element for several organisms and is present in proteins as selenocysteine (Sec or U), an amino acid that is chemically distinct from serine and cysteine by a single atom (Se instead of O or S, respectively). Sec is incorporated into selenoproteins at an in-frame UGA codon specified by an mRNA stem-loop structure called the selenocysteine incorporating sequence (SECIS) presented in selenoprotein mRNA and specific selenocysteine synthesis and incorporation machinery. Selenoproteins are presented in all domains but are not found in all organisms. Although several functions have been attributed to this class, the majority of the proteins are involved in oxidative stress defense. Here, we discuss the kinetoplastid selenocysteine pathway and how selenium supplementation is able to alter the infection course of trypanosomatids in detail. These organisms possess the canonical elements required for selenoprotein production such as phosphoseryl tRNA kinase (PSTK), selenocysteine synthase (SepSecS), selenophosphase synthase (SelD or SPS), and elongation factor EFSec (SelB), whereas other important factors presented in mammal cells, such as SECIS binding protein 2 (SBP) and SecP 43, are absent. The selenoproteome of trypanosomatids is small, as is the selenoproteome of others parasites, which is in contrast to the large number of selenoproteins found in bacteria, aquatic organisms and higher eukaryotes. Trypanosoma and Leishmania are sensitive to auranofin, a potent selenoprotein inhibitor; however, the probable drug mechanism is not related to selenoproteins in kinetoplastids. Selenium supplementation decreases the parasitemia of various Trypanosome infections and reduces important parameters associated with diseases such as anemia and parasite-induced organ damage. New experiments are necessary to determine how selenium acts, but evidence suggests that immune response modulation and increased host defense against oxidative stress contribute to control of the parasite infection.

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The length and the secondary structure of the D-stem of human selenocysteine tRNA are the major identity determinants for serine phosphorylation.

Cited by 26 publications

References 46 publications

Crystal structure of human selenocysteine tRNA

Crystal structure of human selenocysteine tRNA

Identification and characterization of phosphoseryl-tRNA ^[Ser]Sec kinase

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

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The length and the secondary structure of the D-stem of human selenocysteine tRNA are the major identity determinants for serine phosphorylation.

Cited by 26 publications

References 46 publications

Crystal structure of human selenocysteine tRNA

Crystal structure of human selenocysteine tRNA

Identification and characterization of phosphoseryl-tRNA [Ser]Sec kinase

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

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Product

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Identification and characterization of phosphoseryl-tRNA ^[Ser]Sec kinase