Release factors are proteins that play a role in every cell by ensuring the completion of protein synthesis. They signal the end of the protein-building process, allowing the newly formed protein to detach from the cellular machinery. Without their action, proteins would not be the correct length, potentially impairing their function.
Release Factors in Protein Synthesis
Release factors operate in protein synthesis, specifically during translation termination. Translation is the process where genetic information, carried by messenger RNA (mRNA), is used as a blueprint to assemble amino acids into a specific protein chain. This process occurs on ribosomes, the cellular factories for protein production.
As the ribosome moves along the mRNA, reading its genetic code, it continuously adds amino acids to a growing protein chain. Release factors act at the end of this process. They recognize signals indicating the protein chain is complete, ensuring the protein detaches from the ribosome. This detachment is necessary for the protein to fold into its proper three-dimensional shape and carry out its specific functions within the cell.
How Release Factors Terminate Translation
Release factors operate by recognizing specific “stop codons” on the mRNA. These stop codons (UAA, UAG, and UGA) do not code for amino acids; instead, they signal the end of the protein sequence.
When a ribosome encounters a stop codon in its A-site (aminoacyl site), a class 1 release factor binds to the ribosome-mRNA complex. This binding induces a conformational change in the ribosome, activating the peptidyl transferase center. This activation facilitates the hydrolysis (breaking) of the ester bond linking the last amino acid to its transfer RNA (tRNA) in the ribosomal P-site (peptidyl site). This hydrolysis releases the completed polypeptide chain from the ribosome.
After protein release, a class 2 release factor (a GTPase) assists in dissociating and recycling the class 1 release factor from the ribosome. This ensures the ribosomal machinery is ready for a new round of protein synthesis. These coordinated actions ensure accurate and efficient termination, preventing abnormally long or non-functional proteins.
Variations in Release Factors
Release factors vary across life forms, differing between prokaryotic organisms (like bacteria) and eukaryotic organisms (including animals, plants, and fungi). Prokaryotes use two class 1 release factors: RF1 (recognizing UAA and UAG) and RF2 (recognizing UGA and UAA). They also have a class 2 release factor, RF3, a GTPase that helps recycle RF1 and RF2.
Eukaryotic cells use a single class 1 release factor, eRF1, which recognizes all three stop codons (UAA, UAG, and UGA). Eukaryotes also have a class 2 release factor, eRF3, similar to prokaryotic RF3, which is a GTPase that aids in eRF1’s activity and recycling. While their overall function remains consistent, these distinctions highlight evolutionary adaptations in protein synthesis across different domains of life.
When Release Factors Malfunction
Malfunctioning release factors disrupt translation termination, leading to incorrect proteins. If a release factor fails to recognize a stop codon or binds incorrectly, the ribosome may continue adding amino acids beyond the intended termination point, resulting in an abnormally extended protein. Conversely, premature action can release the protein chain too early, leading to a truncated, incomplete protein.
Incorrectly terminated proteins can have significant implications for cellular health and function. They may be non-functional, misfolded, or aggregate into toxic clumps. Such protein errors can contribute to or be associated with various cellular disorders. These errors underscore the precision required for proper protein synthesis and the role of release factors in maintaining cellular integrity.