Translation wobble

Visualize a rotor that has only one imbalance in a single plane. Also, visualize that the plane is not at the rotor s center of gravity, but is off to one side. Although there is no other source of couple, this force to one side of the rotor not only causes translation (parallel motion due to pure static imbalance), but also causes the rotor to rotate or wobble end-over-end as from a couple. In other words, such a force would create a combination of both static and couple imbalance. This again is dynamic imbalance. 

There may be no detectable effect because of the degeneracy of the code. This would be more likely if the changed base in the mRNA molecule were to be at the third nucleotide of a codon such mutations are often referred to as silent mutations. Because of wobble, the translation of a codon is least sensitive to a change at the third position. 

There are 64 different three-letter codons, but we don t have to have 64 different tRNA molecules. Some of the anticodon loops of some of the tRNAs can recognize (bind to) more than one condon in the mRNA. The anticodon loops of the various tRNAs may also contain modified bases that can read (pair with) multiple normal bases in the RNA. This turns out to be the reason for the wobble hypothesis, in which the first two letters of a codon are more significant than the last letter. Look in a codon table and you ll see that changing the last base in a codon often doesn t change the identity of the amino acid. A tRNA that could recognize any base in codon position 3 would translate all four codons as the same amino acid. If you ve actually bothered to look over a codon table, you realize that it s not quite so simple. Some amino acids have single codons (such as AUG for Met), some amino acids have only two codons, and some have four. 

Clearly, the results emerging suggested that at least two nucleotides were modified, the absolute sequence position within the tRNA had yet to be established. Ching etalP showed that a Se U residue was present in the wobble position of the tRNA " from C. sticklandii. This study confirmed a notion that the modification probably affects the translation efficiency of certain transcripts, based on the level of modification by selenium. The authors speculated that the modification to seleno-tRNA (GAG) allowed for more efficient use of this tRNA species as compared to the tRNA (GAA). Even today, no definitive data exist to show that this modification alters the translation efficiency in these bacterial model systems. Nonetheless, these studies had established the chemical forms of Se U and mnm Se U, and established that they were derived from modifications to nucleotides that first required sulfur (S U and mnm S U), the mechanism by which selenium was inserted into the tRNA would not be definitively answered until many years later. 

Many amino acids are specified by more than one codon (redundancy). Frequently, a tRNA can translate more than one of these codons, sparing the ceE from making multiple tRNAs to carry the same amino acid. For instance, in Figure 1-4-6 the arg-tRNA shown can translate both the CGA and the CGG codons that specify arginine. This phenomenon is known as Wobble" and can be summarized as follows ... 

There are not 64 different tRNAs, one for each codon, but instead the tRNAs are capable of unconventional base pairing ( wobble ) with the codons during translation of the mRNA. 

Particles subject to Brownian motion tend to adopt random orientations, and hence do not follow these rules. A particle without these symmetry properties may follow a spiral trajectory, and may also rotate or wobble. In general, the drag and torque on an arbitrary particle translating and rotating in an unbounded quiescent fluid are determined by three second-order tensors which depend on the shape of the body ... 

Terms in bold are defined aminoacyl-tRNA 1035 aminoacyl-tRNA synthetases 1035 translation 1035 codon 1035 reading frame 1036 initiation codon 1038 termination codons 1038 open reading frame (ORF) 1039 anticodon 1039 wobble 1041... 

The 3 terminal redundancy of the genetic code and its mechanistic basis were first appreciated by Francis Crick in 1966. He proposed that codons and anticodons interact in an antiparallel manner on the ribosome in such a way as to require strict Watson-Crick pairing (that is, A-U and G-C) in the first two positions of the codon but to allow other pairings in its 3 terminal position. Nonstandard base pairing between the 3 terminal position of the codon and the 5 terminal position of the anticodon alters the geometry between the paired bases Crick s proposal, labeled the wobble hypothesis, is now viewed as correctly describing the codon-anticodon interactions that underlie the translation of the genetic code. 

A careful comparison of the wobble rules with the genetic code indicates that the minimum number of tRNAs required to translate all 61 codons is 31. With the addition of tRNAjMet the total comes to 32. Most cells contain many more than this minimum number of tRNA types. 

During translation, the anticodon (on tRNA) and the codon (on mRNA) are arranged in the form of a short antiparallel double helix of the Watson-Crick type so that the base in 3 -position of the codon forms a base pair with the base in S -position of the anticodon. Because the number of tRNA s (and the number of anticodons) is limited, the same tRNA anticodon has to base-pair with several of the possible mRNA codons which differ in their 3 -position. Nature solves this problem by allowing nonstandard (wobble) base pairs ... 

The number of mammalian mitochondrial tRNA molecules is 22, which is less than the minimum number (32) needed to translate the universal code. This is possible because in each of the fourfold redundant sets—e.g., the four alanine codons GCU, GCC, GCA, and GCG—only one tRNA molecule (rather than two, as explained above) is used. In each set of four tRNA molecules, the base in the wobble position of the anticodon is U or a modified U (not I). It is not yet known whether this U is base-paired in the codon-anticodon interaction or manages to pair weakly with each of the four possible bases. For those codon sets that are doubly redundant—e.g., the two histidine codons CAU and CAC—the wobble base always forms, a G-U pair, as in the universal code. The structure of the human mitrochondrial tRNA molecule is also different from that of the standard tRNA molecule (except for mitochondrial tRNA UUX). (X = any nucleotide.) The most notable differences are the following ... 

The genetic code is translated through base pairing interactions between mRNA codons and rRNA anticodons. The wobble hypothesis explains why cells usually have fewer tRNAs than expected. 

A careful examination of the genetic code and the wobble rules indicates that a minimum of 31 tRNAs are required to translate all 61 codons. An additional tRNA for initiating protein synthesis brings the total to 32 tRNAs. 

Until recently, the only deviations from the genetic code in eukaryotes were found in mitochondria and chloroplast, where some codons are different and the wobble position is even more flexible (mitochondria use only 24 types of tRNA to translate 13 mitochondrial proteins). However, three phenomenon, translational frameshifting, RNA editing, and protein splicing, remind us that nature is full of surprises. 

Our laboratory has systematically studied the mnm s U and mcm s U wobble position modifications in order to understand how these modifications affect tRNA structure and how structural changes are related to fiinction. " The 2-thio modification is important for stacking stabilization, especially in the tRNA UUU anticodon where the consecutive Us are very poor stackers. This modification alone is sufficient to provide sufficient affinity for tRNA to bind programed ribosomes, and for the tRNA to support translation in The function of the mnm and mcm side chain modifications is to restrict the conformational space... 

Tricyclic hypermodified nucleosides are found in archaeal and eukaryotic tRNAs and are frequently observed at position 34 (wobble base) or position 37 (adjacent to the anticodon). Position 37 typically contains a hypermodified nucleoside such as N -threonylcarbamoyladenosine (t A), 2-methylthio-N -isopentenyl-ade-nosine (ms i A-37), or wybutosine (yW). yW and its derivatives occur at position 37 in archaeal and eukaryotic phenylalanine tRNA (tRNAphe). The modifications serve to maintain the correct translational reading frame via hydrophobic interactions, which reinforce codon—anticodon pairing and prevent incorrect Watson—Crick base-pairing. Studies have shown that unmodified tRNA leads to translational defects that have been implicated in different pathological states. ... 

The tRNA genes (30-33) identified in cpDNA code for functional tRNAs, which form the typical clovcrlcaf structure. It is of particular imerest that tRNA (UUQ not only participates in protein synthesis, but also acts as a cofactor for the formation of 5-aminolevulinic acid, which is a common precursor in heme and chlorophyll biosynthesis. cpDNA-encoded tRNAs suffice for translation of 61 codons if normal wobble base pairing occurs in codon-anticodon recognition. Although this hypothesis is experimentally supported, transport of the nuclear-encoded tRNA into the chloroplasts cannot be excluded. Thus, the Epifagus plastid DNA contains only 17 tRNA genes, which is indirect evidence for the transport of nuclear-encoded tRNAs involved in translation. ... 

Transfer RNA from all organisms contains modified nucleosides. Most of them play an important role in the fine tuning of tRNA activity. The presence of a modified nucleoside improves the efficiency of the tRNA in the decoding event, and may affect the fidelity of protein synthesis and codon choice such as the modified nucleoside next to the 3 -side of the anticodon (position 37) and at the Wobble position (position 34). Modified nucleosides in the anticodon region, other than positions 34 and 37, may influence the translational efficiency and fidelity, whereas those outside the anticodon region may stabilize tRNA conformations. Useful information concerning modified nucleosides in RNA is available from RNA modification database at http //medlib.med.utah.edu/RNAmods. 

In order to synthesise proteins, mitochondria require ribosomes, together with a full complement of tRNAs. To use all of the codons, making allowance for wobble in the third position of the codon, it would be expected that 32 different tRNAs would be required. Mitochondrial translation apparatus has been found not only to have slightly different codon usage (see Table 8.5) but also to use a more extensive wobble ( superwobble ) than the cytoplasmic system, and this enables them to incorporate all the amino acids with only 22 tRNAs. 

Unambiguous. Each codon encodes only one amino acid. An exception is in prokaryotes. The translation start signal is N-formylmethionine (fMet). This enters the ribosome at the P-site (Chapter 70) where it is subject to wobble on the first position of the codon (Chapter 68). Thus, although AUG is the major start codon, a significant number of genes start with GUG, UUG or CUG). In both pro- and eukaryotes, AUG codes for all methionine molecules within the subsequent reading frames. 

The RECE experiments have demonstrated many macroscopic aspects of electron-ring CT s. Compression, translation, merging of two rings, and stability have been demonstrated. In particular, no tilt or wobble instability has been seen and the precessional instability could be stabilized by conducting walls or weak quadrupole fields. Presently, heating and confinement of plasma by the rings is under investigation. 

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