Polypeptide chain termination terminator codons

Polypeptide chain termination and stop codon readthrough on eukaryotic ribosomes... 

Simplicity argues that the genetic blueprint specifying amino acid sequences in proteins should consist of consecutive, nonoverlapping triplets. This assumption turned out to be correct, as is illustrated by the DNA sequence for a gene shown in Fig. 5-5. In addition to the codons that determine the sequence of amino acids in the protein, there are stop codons that tell the ribosomal machinery when to terminate the polypeptide chain. One methionine codon serves as an initiation codon that marks the beginning of a polypeptide sequence. One of the valine codons sometimes functions in the same way. 

NONSENSE CODON A codon that does not specify any amino acid in protein synthesis, but instead specifies termination of a polypeptide chain the nonsense codons are UAA, UAG, and UGA. 

Termination. When a chain termination codon is reached, no aminoaeyl tRNA is available that can fill the A site, so chain elongation stops. Since the polypeptide chain is still attached to the tRNA oeeupying the P site, release of the protein is... 

Premature stop codon polymorphisms, in which there is premature termination of the polypeptide chain by a stop codon (specific sequence of three nucleotides that do not code for an amino acid but rather specify polypeptide chain termination)... 

There are also codons for protein synthesis initiation (AUG) and polypeptide chain termination (UAG, UGA, and UAA). 

Diagrammatic representation of translation on prokaryotic ribosomes. The elongation cycle starts by interaction of the 70S initiation complex with fMet- tRNA EFTu GTP. In all subsequent rounds of the cycle, fMet-tRNArEFT tGTP interacts with the mRNA ribosome complex carrying the growing polypeptide chain. Termination occurs when n amino acids have been incorporated, where n represents the number of codons between the initiation codon AUG and the termination codon (in this example UAA). 

Termination of growth of the peptide chain is signaled by specific codons (UAA, UAG, and UGA) in the mRNA at the A site of the ribosome, and release requires a soluble protein factor, RF. In the process, the peptidyl-tRNA occupying the P or D site is hydrolyzed, liberating the polypeptide. These termination codons are the so-called nonsense codons. 

Elongation continues until the A site is occupied by one of the three stop codons. Since there are no tRNAs with corresponding anticodons, chain termination occurs, with release of the completed polypeptide. 

Termination Three codons (UAA, UAG and UGA) are stop codons which do not code for any amino acid but, instead of attaching to a tRNA molecule, they bind a protein release factor. When one of these factors is encountered by the ribosome, peptidyl transfer is aborted, the completed polypeptide chain released by hydrolysis and the ribosome subunits separate. The N-terminal methionine unit is then removed from the polypeptide chain. 

The ribosome can carry two aminoacyl-tRNAs simultaneously. In the chain elongation stage, the growing polypeptide is carried on one of these tRNAs. The chain is transferred to the second tRNA, which adds its amino acid to the growing peptide, and displaces the first tRNA. The ribosome then moves one codon along the mRNA to allow the next to be read. Termination of protein synthesis involves the release of the completed polypeptide, expulsion of the last tRNA, and dissociation of the ribosome from the mRNA. This is signaled by specific termination codons (UAA, UAG, or UGA) in the mRNA and requires the participation of various release factors. 

Stags 4 Termination and Release Completion of the polypeptide chain is signaled by a termination codon in the mRNA. The new polypeptide is released from the ribosome, aided by proteins called release factors. 

The pathway of protein synthesis translates the three-letter alphabet of nucleotide sequences on mRNA into the twenty-letter alphabet of amino acids that constitute proteins. The mRNA is translated from its 5 -end to its 3 -end, producing a protein synthesized from its amino-terminal end to its carboxyl-terminal end. Prokaryotic mRNAs often have several coding regions, that is, they are polycistronic (see p. 420). Each coding region has its own initiation codon and produces a separate species of polypeptide. In contrast, each eukaryotic mRNA codes for only one polypeptide chain, that is, it is monocistronic. The process of translation is divided into three separate steps initiation, elongation, and termination. The polypeptide chains produced may be modified by posttranslational modification. Eukaryotic protein synthesis resembles that of prokaryotes in most details. [Note Individual differences are mentioned in the text.]... 

The start of protein synthesis is signalled by specific codon-anticodon interactions. Termination is also signalled by a codon in the mRNA, although the stop signal is not recognized by tRNA, but by proteins that then trigger the hydrolysis of the completed polypeptide chain from the tRNA. Just how the secondary and tertiary structures of the proteins are achieved is not yet clear, but certainly the mechanism of protein synthesis, which we have outlined here, requires little modification to account for preferential formation of particular conformations. 

Termination is triggered when the ribosome reaches a stop codon on the mRNA. At this stage, the polypeptide chain is released and the ribosomal subunits dissociate from the mRNA. Various protein factors are involved in all three phases of protein biosynthesis. 

Question Is there an analogous codon that defines the termination site on the mRNA with respect to polypeptide chain formation ... 

At the ribosome, which travels along the mRNA, the tRNA molecule is bound such that its anticodon can interact with a nucleotide triplet on mRNA (the codon). If the anticodon is complementary to a codon triplet on the mRNA, the amino acid attached at the 3 -terminus of the tRNA is transferred to the amino terminus of the growing polypeptide chain if it is not complementanty, the tRNA is rejected and another one is checked for complementary. The whole process is repeated until the synthesis of the protein is completed. It is initiated, as well as terminated, by specific codons regulating this translation. 

Virtually all proteins expressed in cells undergo processing to remove the N-terminal methionine residue encoded by the start codon , ATG. Cleavage of this initiation methionine from newly formed polypeptide chains is catalyzed by the enzyme methionine aminopeptidase (equation 9). 

Once protein synthesis is initiated, amino acids are added to the peptide chain corresponding to each triplet in the mRNA until the ribosome encounters a termination or stop codon, whereupon the polypeptide chain is released from the ribosome, and assumes its final configuration. A ribosome covers about 50 bases of an mRNA, which is usually hundreds of bases long. Thus, several ribosomes translate an mRNA consecutively and simultaneously at any instant as shown in Fig. 2.4. A group of ribosomes translating a message is called a polyribosome . 

The final phase of translation is termination. How does the synthesis of a polypeptide chain come to an end when a stop codon is encountered Aminoacyl-tRNA does not normally bind to the A site of a ribosome if the codon is UAA, UGA, or UAG, because normal cells do not contain tRNAs with anticodons complementary to these stop signals. Instead, these stop codons are recognized by release factors (RFs), which are proteins. One of these release factors, RFl, recognizes UAA or UAG. A second factor, RF2, recognizes UAA or UGA. A third factor, RF3, another G protein homologous to EF-Tu, mediates interactions between RFl or RF2 and the ribosome. 

When a stop codon appears at the A site translation is terminated. There are no tRNA s that recognize stop codons. Instead releasing factors, eRF, recogiiize the stop codon. The releasing factors along with peptidyl transferases and GTP catalyze the hydrolysis of the bond between the polypeptide chain and the tRNA. The protein and tRNA disassociate from the P site and the ribosome dissociates into the 40S and 60S subunits releasing the mRNA. 

Most mutations represent the replacement of one base by another a minority is caused by deletions of some base pairs, by frameshift, by polypeptide chain elongation due to mutation of a terminator codon, or by recombinational events with mutation-like effects. The replacement of one base for another is currently indicated by the term single-nucleotide polymorphism, abbreviated as SNP. It occurs at a frequency of roughly one per every 500-1000 base pairs of genomic DNA, which means that most genes carry one or two SNPs, although many are without any functional significance. ... 

Selenium is incorporated into Se-requiring enzymes by the modification of serine. This serine is not modified when it is in the free state or when it occurs in a polypeptide chain. The serine residue in question is modified when it occurs boimd to transfer RNA, that is, eis the aminoacyl-tRNA derivative. Seryl-tRNA is converted to selenocysteinyl-tRNAby the action of selenocysteine synthase (Stur-chler et al, 1993). The codon for selenocysteine is UGA (TGA in DNA UGA in mRNA). The fact that this particular triplet of bases codes for an amino acid is very imusual, as UGA normally is a stop codon. Stop codons occur in mRNA and signal the termination of synthesis of the protein however, in the case of the UGA codons that code for selenocysteine residues, regions of the mRNA that lie beyond the coding sequence somehow convert the UGA from a codon that halts translation to one that codes for selenocysteine (Figure 10.55). The structure of selenocysteine is shown in Figure 10.56. 

When synthesis of the polypeptide is completed, a termination codon (UGA, UAG, or UAA) causes the polypeptide chain to be released. 

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