Translational and post-translational gene regulation
After RNA has been transported to the cytoplasm, it is translated into protein. Control of this process is largely dependent on the RNA molecule. The stability of the RNA will have a large impact on its translation into a protein. As the stability changes, the amount of time that it is available for translation also changes.
The initiation complex and translation rate
Like transcription, translation is controlled by proteins that bind and initiate the process. In translation, the complex that assembles to start the process is referred to as the translation initiation complex.
In eukaryotes, translation is initiated by binding the initiating met-tRNAi to the 40S ribosome. This tRNA is brought to the 40S ribosome by a protein initiation factor, eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein binds to the high-energy molecule guanosine triphosphate (GTP). The tRNA–eIF2-GTP complex then binds to the 40S ribosome. A second complex forms on the mRNA. Several different initiation factors recognize the 5′ cap of the mRNA and proteins bound to the poly-A tail of the same mRNA, forming the mRNA into a loop. The cap-binding protein eIF4F brings the mRNA complex together with the 40S ribosome complex. The ribosome then scans along the mRNA until it finds a start codon AUG. When the anticodon of the initiator tRNA and the start codon are aligned, the GTP is hydrolyzed, the initiation factors are released, and the large 60S ribosomal subunit binds to form the translation complex.
The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly and translation is impeded (Figure 8.10). When eIF-2 remains unphosphorylated, the initiation complex can form normally and translation can proceed.
Figure 8.10: Gene expression can be controlled by factors that bind the translation initiation complex.
Chemical modifications, protein activity, and longevity
Proteins can be chemically modified with the addition of groups including methyl, phosphate, acetyl, and ubiquitin groups. The addition or removal of these groups from proteins regulates their activity or the length of time they exist in the cell. Sometimes these modifications can regulate where a protein is found in the cell – for example, in the nucleus, in the cytoplasm, or attached to the plasma membrane.
Chemical modifications occur in response to external stimuli such as stress, the lack of nutrients, heat, or ultraviolet light exposure. These changes can alter epigenetic accessibility, transcription, mRNA stability, or translation – all resulting in changes in expression of various genes. This is an efficient way for the cell to rapidly change the levels of specific proteins in response to the environment. Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).
The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded (Figure 8.11). One way to control gene expression, therefore, is to alter the longevity of the protein.
Figure 8.11: Proteins with ubiquitin tags are marked for degradation within the proteasome.
1. Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end of a polynucleotide chain.
References:
- Fowler, Samantha, et al. Concepts of Biology. OpenStax College, Rice University, 2013. Download for free at: https://openstax.org/details/books/concepts-biology.
- Clark, Mary, Jung Choi, and Matthew Douglas. Biology 2E. 2018. Access for free at https://openstax.org/details/books/biology-2e.