Protein release factors

During the normal process of termination of translation, stop codons are recognized by protein release factors (RF). Although the details of the process are not fully understood, it is believed that when a termination codon reaches the ribosomal A-site, the RF associates with the ribosomal-mRNA complex, inducing the peptidyl-transferase center to hydrolyze the ester bond of the pepti-... 

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 last step in translation involves the cleavage of the ester bond that joins the now complete peptide chain to the tRNA corresponding to its C-terminal amino acid (fig. 29.19). Termination requires a termination codon, mRNA and at least one protein release factor (RF). The freeing of the ribosome from mRNA during this step requires the participation of a protein called ribosome releasing factor (RRF). 

In E. coli, termination codons that arrive at the A site on the ribosome are recognized by one of three protein release factors, RF-1 recognizes UAA and UAG, and RF-2 recognizes UAA and UGA. The third release factor, RF-3, does not itself recognize termination codons but stimulates the activity of the other two factors. 

The process continues until a stop codon ends up in the A site at which point a protein release factor binds to the stop codon, the peptide (H3N+-fMet-Gly-Ser— HN-CH(R,i)COO )-tRNA bond is hydrolysed, the completed polypeptide is released and the ribosomal subunits separate. 

Termination. During termination the polypeptide chain is released from the ribosome. Translation terminates because a stop codon cannot bind an aminoacyl-tRNA. Instead, a protein releasing factor binds to the A site. Subsequently, pep-tidyl transferase (acting as an esterase) hydrolyzes the bond connecting the now-completed polypeptide chain and the tRNA in the P site. Translation ends as the ribosome releases the mRNA and dissociates into the large and small subunits. 

The factors controlling termination of synthesis are poorly understood it is known that there is a specific ribosomally bound protein release factor which promotes the hydrolysis of the linkage between the tRNA and the newly formed protein. 

A stop signal is required for the termination of protein synthesis. The codons UAA, UAG, and UGA are the stop signals. These codons are not recognized by any tRNAs, but they are recognized by proteins called release factors (Figure 12.15). One of two protein release factors (RF-1 or RF-2) is required, as is GTP, which is bound to a third release factor, RF-3. RF-1 binds to UAA and UAG, and RF-2 binds to UAA and UGA. RF-3 does not bind to any codon, but it does facilitate the activity of the other two release factors. Either RF-1 or RF-2 is bound near the A site of the ribosome when one of the termination codons is reached. The release factor not only blocks the binding of a new aminoacyl-tRNA but also affects the activity of the peptidyl transferase so that the bond... 

When the ribosome encounters a stop codon, the chain is terminated in a process requiring GTP and three protein release factors. 

Chain termination is signalled by one of the three codons UAA, UGA or UAG which do not code for any amino acid and for which there are no tRNAs. Consequently, protein synthesis halts at any of these termination codons. The codon is then recognized by a protein release factor which hydrolyses the nascent polypeptide chain from the peptidyl-tRNA bound at the A site. 

The stop codons (UAA, UAG and UGA) are read not by tRNA but by protein release factors. These occupy the A site of the ribosome and hydrolyse the peptide-tRNA bond. This releases the finished protein from the ribosome. As the protein leaves, so the two subunits of the ribosome separate, and leave the mRNA they are now available to bind another initiator tRNA and begin the process of translation over again. 

Termination and release of the protein from the ribosome requires the presence of a stop codon and the protein release factors. However, protein synthesis can also come to a halt if there is not enough of one of the amino acids bound to tRNA. In this case, the growing peptide chain is not released from the ribosome, but remains, in arrested development, until the required amino acyl tRNA is available. This means that if the intake of one of the essential amino acids is inadequate then, once supplies are exhausted, protein synthesis will come to a halt. 

Protein synthesis stops when a protein release factor (RF) recognizes specific termination signals contained in the RNA sequence. Three stop or nonsense codons have been identified UAG (amber), UAA (ochre), and UGA (opal). [All ciliated protozoa deviate from the universal genetic code by translating either one or two termination codons into Gin or Cys (13).] Chain termination involves the nucleophilic attack by water on the ester bond between the 3 -adenosine of tRNA and the amino acid. 

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