Structural Basis for the Major Role of O-Phosphoseryl-tRNA Kinase in the UGA-Specific Encoding of Selenocysteine

Chiba, Shiho; Itoh, Yuzuru; Sekine, S.; Yokoyama, Shigeyuki

doi:10.1016/j.molcel.2010.07.018

Cited by 51 publications

(71 citation statements)

References 38 publications

(58 reference statements)

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“…To test for possible "overfitting" of that kind, we examined the noncanonical amino acids selenocysteine (Sec) and pyrrolysine (Pyl). Both amino acids are incorporated into proteins by codon dependent translation, co-opting either a stop codon (Pyl; UAG 31,32 ) or a redundant and rarely used serine codon (Sec; AGU [33][34][35] ) to enlarge the genetic code. These noncanonical amino acids involve changes in both the cognate tRNAs and the enzymes that recognize them.…”

Section: Cross-validationmentioning

confidence: 99%

tRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

Carter

Wolfenden

2015

RNA Biology

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The universal genetic code is a translation table by which nucleic acid sequences can be interpreted as polypeptides with a wide range of biological functions. That information is used by aminoacyltRNA synthetases to translate the code. Moreover, amino acid properties dictate protein folding. We recently reported that digital correlation techniques could identify patterns in tRNA identity elements that govern recognition by synthetases. Our analysis, and the functionality of truncated synthetases that cannot recognize the tRNA anticodon, support the conclusion that the tRNA acceptor stem houses an independent code for the same 20 amino acids that likely functioned earlier in the emergence of genetics. The acceptor-stem code, related to amino acid size, is distinct from a code in the anticodon that is related to amino acid polarity. Details of the acceptor-stem code suggest that it was useful in preserving key properties of stereochemically-encoded peptides that had developed the capacity to interact catalytically with RNA. The quantitative embedding of the chemical properties of amino acids into tRNA bases has implications for the origins of molecular biology.

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Section: Cross-validationmentioning

confidence: 99%

tRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

Carter

Wolfenden

2015

RNA Biology

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“…The absence of these interactions makes the tRNA Sec conformation more flexible compared with that of other cytosolic tRNAs. The existence of such flexibility has already been noticed when the available x-ray conformations of the tRNA Sec were compared with each other (5,8). The flexibility provided by the absence of standard tertiary interactions seems to be essential for the tRNA Sec function.…”

Section: Discussionmentioning

confidence: 81%

“…However, it remains unclear how such an extension of the D-stem can be beneficial for the function of the tRNA Sec . In the archaeal and eukaryotic tRNAs Sec , the long D-stem may be important for the phosphorylation of the seryl moiety by O-phosphoseryl-tRNA kinase, an intermediate step required for the successful delivery of the amino acid selenocysteine (7,8). However, in bacteria, this reaction does not exist (9,10), and yet the D-stem of all bacterial tRNA Sec contains 6 base pairs.…”

mentioning

confidence: 99%

The Long D-stem of the Selenocysteine tRNA Provides Resilience at the Expense of Maximal Function

Ishii

Kotlova

Tapsoba

et al. 2013

Journal of Biological Chemistry

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Background:The selenocysteine tRNA (tRNA Sec ) has a uniquely long D-stem containing 6 base pairs. Results: The extended D-stem is not essential for function but is required for stability. Conclusion: Enhanced secondary structure in selenocysteine tRNA compensates for the absence of canonical tertiary interactions. Significance: The flexibility due to the absence of tertiary interactions is required for tRNA Sec function, whereas the enhanced secondary structure compensates for the decreased stability.

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“…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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Structural Basis for the Major Role of O-Phosphoseryl-tRNA Kinase in the UGA-Specific Encoding of Selenocysteine

Cited by 51 publications

References 38 publications

tRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

tRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

The Long D-stem of the Selenocysteine tRNA Provides Resilience at the Expense of Maximal Function

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

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