Structural Biochemistry/Modulation of Translation
Introduction[edit | edit source]
An effective way gene expression can be controlled is by regulating the translation of RNA. By controlling RNA (primarily mRNA) certain genes can be expressed more or less. Since translation is what transforms the RNA into working proteins, control of this is very crucial for gene expression. There are many enzymes in the body with the purpose of regulating gene expression. These enzymes control gene expression in the body by binding to mRNA and creating changes to the mRNA structure to inhibit or promote translation. Examples of these enzymes include ones that are involved in fatty acid metabolism, pyrimidine synthesis, glycolysis and pentose cycle, and the tricarboxylic acid cycle.[1]
Eukaryotic Factor (elF-2)[edit | edit source]
elF-2 is a protein complex that controls the hydrolysis of GTP, a purine nucleoside triphosphate with a structure close to the guanine nucleobase.[2] GTP also works with it by moderating the amount of ADP it releases which is important for controlling translation in eukaryotic cells. elF-2’s close relationship with GTP also regulates translation in that GTP is a key molecule in beginning the translation step. It binds with Met-tRNA which finds the AUG codon start in mRNA and helps begins translation. Control of the GTP with elF-2 can regulate which mRNAs segments will even begin translation which can control gene expression greatly.
Cytosolic Aconitase[edit | edit source]
Cytosolic aconitase is one of the better understood enzymes that participate in gene regulation. It is a multifunctional enzyme will bind to mRNA and regulate the translation and stability of these mRNAs. It contains a cluster made of iron and sulfur which is its prime mechanism and reacts with cells that lack iron. After binding the mRNA cytosolic aconitase will regulate homeostasis processes involving iron (iron uptake, distribution, storage, and consumption) as well as processes that use iron (oxygen-dependent signaling and cell growth).[1]
CPB-1 and FBF[edit | edit source]
CPB-1 (cytoplasm polyadenylation element binding protein) and FBF (fem-3 mRNA binding factor) are both regulators of mRNA translation. They can interact with one another and form a CPB-1•FBF complex, though its function is currently unknown.[3] An example of CPB-1 and FBF controlling gene expression is in hermaphrodite worms. For these worms, they are important during germline development and will help with stem cell maintenance and determining the dominant sex.
GAPDH[edit | edit source]
GAPDH is an enzyme that is able to bind to many types of RNA (many tRNAs, rRNAs, mRNAs, and viral RNA). It responsive to the presence to the molecule NAD+ used in ATP reactions. In the presence of NAD+, GADPH becomes a glycolytic enzyme and does not bind to mRNA as well. In opposite conditions GADPH will become a better regulator of gene expression.
GADPH is also a component of the GAIT (γ-interferon-activated inhibitor of translation) complex which controls the translations of many different mRNAs while responding to y-interferon.[1] This is different from before since it is not playing as active as a role in gene regulation since it is a constituent of another complex. However, GADPH is still a big part of the GAIT complex and contributes a good deal to its function even if its role is more passive than before.
References[edit | edit source]
- ↑ a b c Hentze, Matthias W.; Preiss, Thomas (2010). "The REM phase of gene regulation". Trends in Biochemical Sciences. 35 (8): 423–6. doi:10.1016/j.tibs.2010.05.009. PMID 20554447.
- ↑ Kozak, Marilyn (1999). "Initiation of translation in prokaryotes and eukaryotes". Gene. 234 (2): 187–208. doi:10.1016/S0378-1119(99)00210-3. PMID 10395892.
- ↑ Menichelli, Elena; Wu, Joann; Campbell, Zachary T.; Wickens, Marvin; Williamson, James R. (2013). "Biochemical Characterization of the Caenorhabditis elegans FBF⋅CPB-1 Translational Regulation Complex Identifies Conserved Protein Interaction Hotspots". Journal of Molecular Biology. 425 (4): 725–37. doi:10.1016/j.jmb.2012.11.012. PMC 3568192. PMID 23159558.