Translational regulation
From Wikipedia, the free encyclopedia
Translational regulation refers to the control of the levels of protein synthesized from its mRNA. This regulation is vastly important to the cellular response to stressors, growth cues, and differentiation. In comparison to transcriptional regulation, it results in much more immediate cellular adjustment through direct regulation of protein concentration. The corresponding mechanisms are primarily targeted on the control of ribosome recruitment on the initiation codon, but can also involve modulation of peptide elongation, termination of protein synthesis, or ribosome biogenesis. While these general concepts are widely conserved, some of the finer details in this sort of regulation have been proven to differ between prokaryotic and eukaryotic organisms.
Initiation
Initiation of translation is regulated by the accessibility of ribosomes to the Shine-Dalgarno sequence. This stretch of four to nine purine residues are located upstream the initiation codon and hybridize to a pyrimidine-rich sequence near the 3' end of the 16S RNA within the 30S bacterial ribosomal subunit.[1] Polymorphism in this particular sequence has both positive and negative effects on the efficiency of base-pairing and subsequent protein expression.[2] Initiation is also regulated by proteins known as initiation factors which provide kinetic assistance to the binding between the initiation codon and tRNAfMet, which supplies the 3'-UAC-5' anticodon. IF1 binds the 30S subunit first, instigating a conformational change[3] that allows for the additional binding of IF2 and IF3.[4] IF2 ensures that tRNAfMet remains in the correct position while IF3 proofreads initiation codon base-pairing to prevent non-canonical initiation at codons such as AUU and AUC.[5] Generally, these initiation factors are expressed in equal proportion to ribosomes, however experiments using cold-shock conditions have shown to create stoichiometric imbalances between these translational machinery. In this case, two to three fold changes in expression of initiation factors coincide with increased favorability towards translation of specific cold-shock mRNAs.[6]
Elongation
Due to the fact that translation elongation is an irreversible process, there are few known mechanisms of its regulation. However, it has been shown that translational efficiency is reduced via diminished tRNA pools, which are required for the elongation of polypeptides. In fact, the richness of these tRNA pools are susceptible to change through cellular oxygen supply.[7]
Termination
The termination of translation requires coordination between release factor proteins, the mRNA sequence, and ribosomes. Once a termination codon is read, release factors RF-1, RF-2, and RF-3 contribute to the hydrolysis of the growing polypeptide, which terminates the chain. Bases downstream the stop codon affect the activity of these release factors. In fact, some bases proximal to the stop codon suppress the efficiency of translation termination by reducing the enzymatic activity of the release factors. For instance, the termination efficiency of a UAAU stop codon is near 80% while the efficiency of UGAC as a termination signal is only 7%.[8]
