Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl‐tRNA formation systems

Yuan, Jing; O’Donoghue, Patrick; Ambrogelly, Alex; Gundllapalli, Sarath; Sherrer, R. Lynn; Palioura, Sotiria; Simonović, Miljan; Söll, Dieter

doi:10.1016/j.febslet.2009.11.005

Cited by 72 publications

(64 citation statements)

References 68 publications

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“…We focus on tRNA Sec , the UGA-specific tRNA that carries the amino acid selenocysteine into selenoproteins in archaea, eukaryotes, and certain bacteria (Yuan et al 2010). tRNA Sec is the largest among known mature tRNA species with a long variable arm and an extended acceptor arm ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Human tRNA^Secassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers

Janas

Yarus

2012

RNA

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We have shown previously that simple RNA structures bind pure phospholipid liposomes. However, binding of bona fide cellular RNAs under physiological ionic conditions is shown here for the first time. Human tRNA Sec contains a hydrophobic anticodon-loop modification: N 6 -isopentenyladenosine (i 6 A) adjacent to its anticodon. Using a highly specific double-probe hybridization assay, we show mature human tRNA Sec specifically retained in HeLa intermediate-density membranes. Further, isolated human tRNA Sec rebinds to liposomes from isolated HeLa membrane lipids, to a much greater extent than an unmodified tRNA Sec transcript. To better define this affinity, experiments with pure lipids show that liposomes forming rafts or including positively charged sphingosine, or particularly both together, exhibit increased tRNA Sec binding. Thus tRNA Sec residence on membranes is determined by several factors, such as hydrophobic modification (likely isopentenylation of tRNA Sec ), lipid structure (particularly lipid rafts), or sphingosine at a physiological concentration in rafted membranes. From prior work, RNA structure and ionic conditions also appear important. tRNA Sec dissociation from HeLa liposomes implies a mean membrane residence of 7.6 min at 24°C (t 1 ⁄ 2 = 5.3 min). Clearly RNA with a 5-carbon hydrophobic modification binds HeLa membranes, probably favoring raft domains containing specific lipids, for times sufficient to alter biological fates.

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Section: Introductionmentioning

confidence: 99%

Human tRNA^Secassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers

Janas

Yarus

2012

RNA

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“…However, we now know of natural code expansion with selenocysteine and pyrrolysine (11). One organism, Acetohalobium arabaticum, dynamically varies the number of amino acids it encodes between 20 and 21, depending on its carbon source (12).…”

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confidence: 99%

UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota

Campbell

O’Donoghue²,

Campbell

et al. 2013

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

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The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA Gly UCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA Gly UCA with glycine in vitro with similar activity compared with normal tRNA Gly UCC . Coexpression of SR1 glycyl-tRNA synthetase and tRNA Gly UCA in Escherichia coli yields significant β-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.

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“…The enzyme charges phosphoserine (Sep) onto tRNA Cys and the resulting Sep-tRNA Cys is used as the substrate for a tRNA dependent modifi cation of phosphoserine into cysteine (O'Donoghue et al 2005 ;Sauerwald et al 2005 ). It is worth mentioning that there is yet a 23rd aaRS, which catalyzes the pyrrolysylation (Pyl) of an unusual UAG-decoding tRNA in certain bacteria and archaea: the pyrrolysyl-tRNA synthetase (PylRS) (Polycarpo et al 2004 ;Herring et al 2007 ;Yuan et al 2010 ). The 23 aaRSs are split almost equally into two classes (class I and class II) based mainly on the structure of their active site domains and location of the active site where adenosine triphosphate (ATP) is bound.…”

Section: Aminoacyl-trna Synthetasesmentioning

confidence: 99%

Highlights on Trypanosomatid Aminoacyl-tRNA Synthesis

Polycarpo

2013

Subcellular Biochemistry

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Aminoacyl-tRNA synthetases aaRSs are responsible for the aminoacylation of tRNAs in the first step of protein synthesis. They comprise a group of enzymes that catalyze the formation of each possible aminoacyl-tRNA necessary for messenger RNA decoding in a cell. These enzymes have been divided into two classes according to structural features of their active sites and, although each class shares a common active site core, they present an assorted array of appended domains that makes them sufficiently diverse among the different living organisms. Here we will explore what is known about the diversity encountered among trypanosomatids' aaRSs that has helped us not only to understand better the biology of these parasites but can be used rationally for the design of drugs against these protozoa.

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Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl‐tRNA formation systems

Cited by 72 publications

References 68 publications

Human tRNA^Secassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers

Human tRNA^Secassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers

UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota

Highlights on Trypanosomatid Aminoacyl-tRNA Synthesis

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Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl‐tRNA formation systems

Cited by 72 publications

References 68 publications

Human tRNASecassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers

Human tRNASecassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers

UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota

Highlights on Trypanosomatid Aminoacyl-tRNA Synthesis

Contact Info

Product

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About

Human tRNA^Secassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers

Human tRNA^Secassociates with HeLa membranes, cell lipid liposomes, and synthetic lipid bilayers