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1.
Degeneracy of the genetic code was attributed by Crick to imprecise hydrogen-bonded base-pairing at the wobble position during codon–anticodon pairing. The Crick wobble rules define but do not explain the RNA base pair combinations allowed at this position. We select six pyrimidine bases functioning as anticodon wobble bases (AWBs) to study their H-bonded pairing properties with the four major RNA bases using density functional theory at the B3LYP/6-31G(d,p) level. This is done to assess the extent to which the configuration of a solitary RNA wobble base pair may in itself determine specificity and degeneracy of the genetic code by allowing or disallowing the given base pair during codon–anticodon pairing. Calculated values of select configuration markers for the base pairs screen well between allowed and disallowed base pairs for most cases examined here, where the base pair width emerges as an important factor. A few allowed wobble pairs invoke the involvement of RNA nucleoside conformation, as well as involvement of the exocyclic substituent in H-bonding. This study, however, cannot explain the disallowed status of the Ura?Gua wobble pair on the basis of configuration alone. Explanation of the allowed status of the V?Ura pair requires further study on the mediatory role of water molecules. Apart from these two cases, these computational results are sufficient, on the basis of base pair configuration alone, to account for the specificity and degeneracy of the genetic code for all known cases of codon–anticodon pairing which involve the pyrimidine AWBs studied here.  相似文献   

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3.
P F Agris 《Biochimie》1991,73(11):1345-1349
While recognized that some wobble exists in the base pairing of the first base of the tRNA anticodon with the third of the codon, specific base modifications have evolved to select particular codons. This modified-wobble theory would be exemplified by a single codon recognition imposed on the anticodon by modification of the tRNA wobble position nucleoside.  相似文献   

4.
Crick's wobble theory states that some specific pairs between the bases at the first position of the anticodon (position 34) and the third position of the codon (position III) are allowed and the others are disallowed during the correct codon recognition. However, later researches have shown that the pairing rule, or the wobble rule, is different from the supposed one. Despite the continuing efforts including computer-aided model building studies and analyses of three-dimensional structures in the crystals of the ribosomes, the structural backgrounds of the wobble rule are still unclear. Here, I classify the possible pairs into 6 classes according to the increases accompanying the formation of the pairs in the potential productivity of the decoding complex on the basis of a simple model that was originally proposed previously and is refined here. In the model, the conformation with the base at position 34 displaced toward the minor groove side from the position for the Watson-Crick pairs is supposed to be equivalent to the conformation with the Watson-Crick pairs. It is also reasoned and supposed that some weak pairs may sometimes be allowed depending on the structural context. It is demonstrated that most of the experimental results reported so far are consistent with the model. I discuss on which experimental facts can be reasoned with the model and which need further explanations. I expect that the model will be a good basis for further understanding of the wobble rule and its structural backgrounds.  相似文献   

5.
Alanine is encoded by the four codons of the GC box (GCA, GCG, GCU, and GCC). Known alanine anticodons include the UGC, IGC, and VGC triplets (I = inosine; V = uridine-5-oxyacetic acid). The energy-minimized structures of all possible codon–anticodon combinations involving all the alanine codons GCA, GCG, GCU, and GCC with the alanine anticodons UGC, IGC, and VGC are studied using the AMBER software. Fifteen H-bonded duplex structures arising out of these combinations are studied here, all having Watson–Crick-type base pairs at the first and second codon positions, and a variety of base pairing possibilities at the third (or wobble) position. Structural and stability considerations suggest that some codon–anticodon duplexes would be more favored than others for accommodation during the translation process. The UGC anticodon is predicted to favor the GCA codon for reading, while the GCC codon is least favored. The IGC anticodon would prefer to read the GCC codon, the GCG codon being least favored, while a syn conformer for A in the GCA codon could allow for it to be read. For the VGC anticodon, the GCA codon is predicted to be read most favorably, and the GCC codon least favorably, while a syn conformer for V in the anticodon would allow for the codon GCU to be read through a wobble pair which involves the exocyclic 5-oxyacetate group of V in H-bonding.  相似文献   

6.
Two alternative hypotheses aim to predict the wobble nucleotide of tRNA anticodons in mitochondrion. The codon-anticodon adaptation hypothesis predicts that the wobble nucleotide of tRNA anticodon should evolve toward maximizing the Watson-Crick base pairing with the most frequently used codon within each synonymous codon family. In contrast, the wobble versatility hypothesis argues that the nucleotide at the wobble site should be occupied by a nucleotide most versatile in wobble pairing, i.e., the wobble site of the tRNA anticodon should be G for NNY codon families and U for NNR and NNN codon families (where Y stands for C or U, R for A or G, and N for any nucleotide). We examined codon usage and anticodon wobble sites in 36 fungal genomes to evaluate these two alternative hypotheses and identify exceptional cases that deserve new explanations. While the wobble versatility hypothesis is generally supported, there are interesting exceptions involving tRNA(Arg) translating the CGN codon family, tRNA(Trp) translating the UGR codon family, and tRNA(Met) translating the AUR codon family. Our results suggest that the potential to suppress stop codons, the historical inertia, and the conflict between translation initiation and elongation can all contribute to determining the wobble nucleotide of tRNA anticodons.  相似文献   

7.
This study investigates bypassing initiated from codons immediately 5' of a stop codon. The mRNA slips and is scanned by the peptidyl-tRNA for a suitable landing site, and standard decoding resumes at the next 3' codon. This work shows that landing sites with potentially strong base pairing between the peptidyl-tRNA anticodon and mRNA are preferred, but sites with little or no potential for Watson-Crick or wobble base pairing can also be utilized. These results have implications for re-pairing in ribosomal frameshifting. Shine-Dalgarno sequences in the mRNA can alter the distribution of landing sites observed. The bacteriophage T4 gene 60 nascent peptide, known to influence take-off in its native context, imposes stringent P-site pairing requirements, thereby limiting the number of suitable landing sites.  相似文献   

8.
He G  Kwok CK  Lam SL 《FEBS letters》2011,585(24):3953-3958
It has long been recognized that T·T mismatches can adopt two different modes of exchangeable wobble base pairs in which no preferential pairing mode has been observed. In this study, we have performed a systematic nuclear magnetic resonance (NMR) investigation to study the sequence context effect on the pairing modes of T·T mismatches. Our results reveal for the first time that preferential pairing mode does exist in T·T mismatches with specific type of flanking base pairs.  相似文献   

9.
The DNA oligomer d(CGCGTG) crystallizes as a Z-DNA double helix containing two guanine-thymine base pair mismatches of the wobble type. The crystal diffracts to 1 A resolution and the structure has been solved and refined. At this resolution, a large amount of information is revealed about the organization of the water molecules in the lattice generally and more specifically around the wobble base pairs. By comparing this structure with the analogous high resolution structure of d(CGCGCG) we can visualize the structural changes as well as the reorganization of the solvent molecules associated with wobble base pairing. There is only a small distortion of the Z-DNA backbone resulting from introduction of the GT mismatched base pairs. The water molecules cluster around the wobble base pair taking up all of the hydrogen bonding capabilities of the bases due to wobble pairing. These bridging water molecules serve to stabilize the base-base interaction and, thus, may be generally important for base mispairing either in DNA or in RNA molecules.  相似文献   

10.
By utilizing an enzymatically reconstructed tRNA variant containing an altered anticodon sequence, we have examined the different biochemical behavior of translation between the Watson-Crick type and the wobble type base pair interactions at the first anticodon position. We have found that the Watson-Crick type base pair has an advantage in translation in contrast to the wobble type base pair by comparing the efficiency of transpeptidation of native tRNA(Phe) (anticodon; GmAA) with its variant tRNA (anticodon; AAA) in the poly(U)-programmed ribosome system. Thomas et al. [Proc. Natl. Acad. Sci. U.S. (1988) 85, 4242-4246] showed that the wobble codon at the ribosomal A-site accepted its cognate tRNA less efficiently than the Watson-Crick base pairing codon. We report here that the wobble interaction at the ribosomal P-site also affected the rate of translation. This variable translational rate may be a mechanism of gene regulation through preferential codon usage.  相似文献   

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Decoding the genome: a modified view   总被引:10,自引:4,他引:6       下载免费PDF全文
Transfer RNA’s role in decoding the genome is critical to the accuracy and efficiency of protein synthesis. Though modified nucleosides were identified in RNA 50 years ago, only recently has their importance to tRNA’s ability to decode cognate and wobble codons become apparent. RNA modifications are ubiquitous. To date, some 100 different posttranslational modifications have been identified. Modifications of tRNA are the most extensively investigated; however, many other RNAs have modified nucleosides. The modifications that occur at the first, or wobble position, of tRNA’s anticodon and those 3′-adjacent to the anticodon are of particular interest. The tRNAs most affected by individual and combinations of modifications respond to codons in mixed codon boxes where distinction of the third codon base is important for discriminating between the correct cognate or wobble codons and the incorrect near-cognate codons (e.g. AAA/G for lysine versus AAU/C asparagine). In contrast, other modifications expand wobble codon recognition, such as U·U base pairing, for tRNAs that respond to multiple codons of a 4-fold degenerate codon box (e.g. GUU/A/C/G for valine). Whether restricting codon recognition, expanding wobble, enabling translocation, or maintaining the messenger RNA, reading frame modifications appear to reduce anticodon loop dynamics to that accepted by the ribosome. Therefore, we suggest that anticodon stem and loop domain nucleoside modifications allow a limited number of tRNAs to accurately and efficiently decode the 61 amino acid codons by selectively restricting some anticodon–codon interactions and expanding others.  相似文献   

13.
The structure of the genetic code implies strict Watson–Crick base pairing in the first two codon positions, while the third position is known to be degenerate, thus allowing wobble base pairing. Recent crystal structures of near-cognate tRNAs accommodated into the ribosomal A-site, however, show canonical geometry even with first and second position mismatches. This immediately raises the question of whether these structures correspond to tautomerization of the base pairs. Further, if unusual tautomers are indeed trapped why do they not cause errors in decoding? Here, we use molecular dynamics free energy calculations of ribosomal complexes with cognate and near-cognate tRNAs to analyze the structures and energetics of G-U mismatches in the first two codon positions. We find that the enol tautomer of G is almost isoenergetic with the corresponding ketone in the first position, while it is actually more stable in the second position. Tautomerization of U, on the other hand is highly penalized. The presence of the unusual enol form of G thus explains the crystallographic observations. However, the calculations also show that this tautomer does not cause high codon reading error frequencies, as the resulting tRNA binding free energies are significantly higher than for the cognate complex.  相似文献   

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15.
The tRNA1Ser (anticodon VGA, V=uridin-5-oxyacetic acid) is essential for translation of the UCA codon in Escherichia coli. Here, we studied the translational abilities of serine tRNA derivatives, which have different bases from wild type at the first positions of their anticodons, using synthetic mRNAs containing the UCN (N=A, G, C, or U) codon. The tRNA1Ser(G34) having the anticodon GGA was able to read not only UCC and UCU codons but also UCA and UCG codons. This means that the formation of G-A or G-G pair allowed at the wobble position and these base pairs are noncanonical. The translational efficiency of the tRNA1Ser(G34) for UCA or UCG codon depends on the 2'-O-methylation of the C32 (Cm). The 2'-O-methylation of C32 may give rise to the space necessary for G-A or G-G base pair formation between the first position of anticodon and the third position of codon.  相似文献   

16.
Translation of the isoleucine codon AUA in most prokaryotes requires a modified C (lysidine or agmatidine) at the wobble position of tRNA2Ile to base pair specifically with the A of the AUA codon but not with the G of AUG. Recently, a Bacillus subtilis strain was isolated in which the essential gene encoding tRNAIle-lysidine synthetase was deleted for the first time. In such a strain, C34 at the wobble position of tRNA2Ile is expected to remain unmodified and cells depend on a mutant suppressor tRNA derived from tRNA1Ile, in which G34 has been changed to U34. An important question, therefore, is how U34 base pairs with A without also base pairing with G. Here, we show (i) that unlike U34 at the wobble position of all B. subtilis tRNAs of known sequence, U34 in the mutant tRNA is not modified, and (ii) that the mutant tRNA binds strongly to the AUA codon on B. subtilis ribosomes but only weakly to AUG. These in vitro data explain why the suppressor strain displays only a low level of misreading AUG codons in vivo and, as shown here, grows at a rate comparable to that of the wild-type strain.  相似文献   

17.
RNA is now known to possess various structural, regulatory and enzymatic functions for survival of cellular organisms. Functional RNA structures are generally created by three-dimensional organization of small structural motifs, formed by base pairing between self-complementary sequences from different parts of the RNA chain. In addition to the canonical Watson–Crick or wobble base pairs, several non-canonical base pairs are found to be crucial to the structural organization of RNA molecules. They appear within different structural motifs and are found to stabilize the molecule through long-range intra-molecular interactions between basic structural motifs like double helices and loops. These base pairs also impart functional variation to the minor groove of A-form RNA helices, thus forming anchoring site for metabolites and ligands. Non-canonical base pairs are formed by edge-to-edge hydrogen bonding interactions between the bases. A large number of theoretical studies have been done to detect and analyze these non-canonical base pairs within crystal or NMR derived structures of different functional RNA. Theoretical studies of these isolated base pairs using ab initio quantum chemical methods as well as molecular dynamics simulations of larger fragments have also established that many of these non-canonical base pairs are as stable as the canonical Watson–Crick base pairs. This review focuses on the various structural aspects of non-canonical base pairs in the organization of RNA molecules and the possible applications of these base pairs in predicting RNA structures with more accuracy.  相似文献   

18.
Here we report the crystal structures of I.C and I.A wobble base pairs in the context of the ribosomal decoding center, clearly showing that the I.A base pair is of an I(anti).A(anti) conformation, as predicted by Crick. Additionally, the structures enable the observation of changes in the anticodon to allow purine-purine base pairing, the 'widest' base pair geometry allowed in the wobble position.  相似文献   

19.
An ab initio model for gene prediction in prokaryotic genomes is proposed based on physicochemical characteristics of codons calculated from molecular dynamics (MD) simulations. The model requires a specification of three calculated quantities for each codon: the double-helical trinucleotide base pairing energy, the base pair stacking energy, and an index of the propensity of a codon for protein-nucleic acid interactions. The base pairing and stacking energies for each codon are obtained from recently reported MD simulations on all unique tetranucleotide steps, and the third parameter is assigned based on the conjugate rule previously proposed to account for the wobble hypothesis with respect to degeneracies in the genetic code. The third interaction propensity parameter values correlate well with ab initio MD calculated solvation energies and flexibility of codon sequences as well as codon usage in genes and amino acid composition frequencies in ∼175,000 protein sequences in the Swissprot database. Assignment of these three parameters for each codon enables the calculation of the magnitude and orientation of a cumulative three-dimensional vector for a DNA sequence of any length in each of the six genomic reading frames. Analysis of 372 genomes comprising ∼350,000 genes shows that the orientations of the gene and nongene vectors are well differentiated and make a clear distinction feasible between genic and nongenic sequences at a level equivalent to or better than currently available knowledge-based models trained on the basis of empirical data, presenting a strong support for the possibility of a unique and useful physicochemical characterization of DNA sequences from codons to genomes.  相似文献   

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