Compilation of tRNA sequences and sequences of tRNA genes

Chronic progressive extern al ophthalmoplegia (CPEO) is caused by a decreased oxidative phosphorylation (OXPHOS) activity due to large-scale deletions of the mitochondrial genome in 50 % of the patients. The deletions encompass structural OXPHOS genes as weil as tRNA genes, required for their expression so that the pathogenesis could be due to the deleted OXPHOS subunits or to an impaired mitochondrial translation. We have analyzed the mitochondrial genome of a patient presenting with CPEO for single base substitutions and discovered a novel heteroplasmic mutation in the tRNAA,n gene at position 5692 that converts a highly conserved adenine into a guanine. This mutation is unique because it is located at the transition of the anticodon loop to the anticodon stern and it leads to an additional base pair, thus reducing the number of loop-forming nucleotides from seven to five. Our findings suggest that CPEO can be caused by a single base substition in a mitochondrial tRNA gene so that the mitochondrial protein synthesis becomes the rate limiting step in OXPHOS fidelity.

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“…2a) relative to eonserved stem regions (21). In • this alignment, the A was present in all other species from rat to sea urchin.…”

Section: Resultsmentioning

confidence: 77%

Chronic Progressive External Ophthalmoplegia Is Associated with a Novel Mutation in the Mitochondrial tRNAAsn Gene

Seibel

Lauber

Klopstock

et al. 1994

Biochemical and Biophysical Research Communications

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“…This priming event often is initiated 2 bp downstream from the 5' LTR. The sequence 5'-TGGTAT-CAAAGGTCACCGATCCTGG-3', beginning 2 bp downstream from the BsJ 5' LTR, shares 21 bp of homology with the 3' end of the only initiator methionyl-tRNAs sequenced in plants, those from the monocot wheat and the dicots Lupinous luteus and Phaseolus vulgaris (20,21). The homology observed is found in three interrupted blocks of 8, 4, and 9 bp (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…3), thereby providing a theoretical overall binding energy equivalent to approximately 13 or 14 bp of continuous homology. Initiator methionyl-tRNA sequences are highly conserved in nature (20,21), and it is likely that the maize initiator methionyl-tRNA has an identical 3' sequence. Reverse transcriptions of Ty, copia, and CaMV (22) RNAs are primed by initiator methionyl-tRNAs.…”

Section: Resultsmentioning

confidence: 99%

Structure and coding properties of Bs1, a maize retrovirus-like transposon.

Jin

Bennetzen²

1989

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

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We have sequenced Bs), an insertion element isolated from a null allele of the Adhi locus encoding alcohol dehydrogenase in maize. The Bs) element is 3203 base pairs (bp) in length, has 302-bp identical long terminal direct repeats (LTRs), and created a 5-bp flanking direct duplication oftarget AdhI DNA upon insertion. The 5' LTR is followed by a canonical primer binding site with homology to the plant initiator methionyl-tRNA, and the 3' LTR is directly preceded by a polypurine stretch like that observed in retroviruses and retrotransposons. Bs) encodes two overlapping open reading frames specifying peptides of 740 and 168 amino acids. The longer open reading frame specifies a peptide with amino acid homology to the protease and nucleic acid binding moiety of retroviruses and retrotransposons. The deduced amino acid sequence encoded by Bsl lacks convincing homology to the polymerase (reverse transcriptase) encoded by retroposons, despite the fact that this polymerase-encoding domain is routinely the most conserved region of any such element. The sequence and relatively small size of Bs) suggest that this element is a deleted retrotransposon that inserted into AdhM with the aid of a reverse transcriptase function provided in trans. In vitro transcribed Bsl complementary RNA was translated in vitro to produce both a protein of 81 kDa representing open reading frame 1 (ORF1) and one of the 95-kDa size predicted for the frame-shifted fusion of ORF1 and ORF2. As with many other retroposons, the efficiency of translational initiation at the AUG beginning ORF1 was not noticeably affected by the presence of one or more upstream, unproductive AUGs in the complementary RNA transcript.By both structural and mechanistic criteria, eukaryotic insertion sequences and transposable elements can be divided into two major categories. One class of elements is bounded by inverted terminal repeat sequences and transposes through excision (1, 2) and/or enhanced replication (3) of the integrated element. Examples of this class of transposable elements are the controlling elements of maize (4) and the P elements of Drosophila (5). A second class of eukaryotic insertion sequences, the "retroposons," integrate into the chromosome after reverse transcription of element-encoded RNA (6), are particularly abundant in animals, and are the only type of insertion sequence yet discovered in fungi. Both the retroviruses (6) and the LI elements (7) of vertebrates and the "retrotransposons" Ty of yeast (8) and copia of Drosophila (9) fall into this latter category.Despite the early discovery and characterization of numerous distinct transposable elements in maize (1, 4), a canonical retrovirus or retrotransposon has not been described in plants. The DNA caulimoviruses ofplants have the structural properties and encode the reverse transcriptase activity definitional of a retrovirus or retrotransposon but apparently do not integrate into chromosomal DNA (10). Recently, Schwarz-Sommer et al. (11) have found that the Cin4 insertion element of m...

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“…Pseudoknots were not considered because the program cannot predict them. For tRNA and 5S rRNA, structure predictions were made on 141 and 67 randomly chosen sequences and compared with phylogenetic models (10,38). For tRNA, modified nucleotides unable to base pair were not allowed to pair.…”

Section: Resultsmentioning

confidence: 99%

Improved predictions of secondary structures for RNA.

Jaeger

Turner

Zuker

1989

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

777

538

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The accuracy of computer predictions of RNA secondary structure from sequence data and free energy parameters has been increased to roughly 70%. Performance is judged by comparison with structures known from phylogenetic analysis. The algorithm also generates suboptimal structures. On average, the best structure within 10% of the lowest free energy contains roughly 90% of phylogenetically known helixes. The algorithm does not include tertiary interactions or pseudoknots and employs a crude model for singlestranded regions. The only favorable interactions are base pairing and stacking of terminal unpaired nucleotides at the ends of helixes. The excellent performance is consistent with these interactions being the primary interactions determining RNA secondary structure.RNA is important for functions such as catalysis, RNA splicing, regulation of transcription and translation, and transport of proteins across membranes (1). Many RNA sequences are known. Determination of secondary structures, however, is difficult. Thermodynamics has been applied to predict RNA secondary structure from sequence (2, 3), but with modest success. Predictions of suboptimal structures make the method more useful (4). We report combining several recent advances to improve predictions of RNA secondary structures. Three advances are incorporated in this work. (i) New methods for synthesizing RNA make it possible to obtain model systems with a large variety of sequence (5, 6). This technique has led to measurements of improved parameters and the realization that non-base-paired nucleotides contribute sequence-dependent interactions that stabilize secondary structure (7, 8). (ii) A computer algorithm has been developed that allows incorporation of non-base-paired interactions in the prediction of optimal and suboptimal secondary structures (9). (iii) Several RNA secondary structures have been determined by phylogeny (10-15). Comparison of predicted and known structures allows optimization of parameters that have not been measured. Resultant predictions appear sufficiently reliable to aid planning and interpretation of experiments on RNA. MATERIALS AND METHODSThermodynamic Parameters. When possible, free energy increments at 370C, AG037, were taken from experiments in 1 M NaCl. For fully base-paired regions, experiments on dGCATGC indicate that 1 M NaCl mimics solutions containing 1-100 mM Mg2+ in the presence of 0.15-1 M NaCl (16).Relatively few experiments are available for loop structures, and, therefore, little is known about interactions determining loop stability. This situation forced approximations. (i) Jacobson-Stockmayer theory (17) was used to extrapolate the length dependence of AG37 for bulge, hairpin, and internal loops: AG0(n) = AG(nmax) + 1.75 RTln (n/nmax).For this equation n is the number of unpaired nucleotides in the loop, nma is the maximum-length loop for which experimental data is available, R is the gas constant (1.987 cal mol'lK-l; 1 cal = 4.184 J), and T is the temperature in K (310.15 K for 370C). (ii) When...

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Compilation of tRNA sequences and sequences of tRNA genes

Cited by 209 publications

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Chronic Progressive External Ophthalmoplegia Is Associated with a Novel Mutation in the Mitochondrial tRNAAsn Gene

Chronic Progressive External Ophthalmoplegia Is Associated with a Novel Mutation in the Mitochondrial tRNAAsn Gene

Structure and coding properties of Bs1, a maize retrovirus-like transposon.

Improved predictions of secondary structures for RNA.

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