Organisms are composed of numerous cells. Depending on where they are, the cells express different functions by synthesizing different proteins. Although the genome inside the cells has abilities to express all kinds of proteins, the types and amounts of proteins expressed are strictly controlled by at multiple levels; (1) controlling when and how often a given gene is transcribed (transcription control), (2) controlling how the RNA transcript is spliced or otherwise processed (RNA processing control), (3) selecting which completed mRNAs in the cell nucleus are exported to the cytosol and determining where in the cytosol they are localized (RNA transport and localizing control), (4) selecting which mRNAs in the cytoplasm are translated by ribosomes (translational control), (5) destabilizing certain mRNA molecules in the cytoplasm (mRNA degradation control), or (6) activating, inactivating, degrading, or compartmentalizing specific protein molecules after they have been made (protein activity control).
For most genes transcriptional controls are predominant. Only transcriptional control ensures that the cell will not synthesize superfluous intermediates. Once an mRNA has been synthesized, one of the most common ways to regulating the level of its protein product is by translation control (above 4). Diverse set of metabolites including small organic molecule, amino acids, nucleobases and proteins bind to mRNA for pausing translation to produce proteins
The structure shown here is an example that small organic molecule (S-adenosylmethonine (SAM)) binds to the 5'-untranslated regions of Thermoanaerobacter tengcongensis mRNA, an RNA element that controls the expression of several genes involved in sulphur and methionine metabolism, to terminate translation. Regulation is done through the interplay between two domains of the RNA: an aptamer domain that responds to intercellular metabolite concentration (when metabolites are too abundant, they bind to this domain), and an expression platform that uses mutually exclusive secondary structures to direct a decision-making process. The aptamer domain is established through two sets of coaxially stacked helices, and ligand-binding pocket is situated between them. SAM adapts a compact conformation in which the methionine moiety stacks upon the adenine ring, although SAM adapts an extended trans configuration in the most proteins. It is revealed that the interaction between SAM and the mRNA induces a series of tertiary interactions including hydrogen-bonding interaction between backbone ribose-phosphate groups and van der Waals interactions between two ribose sugars, causing prevention of antiterminator element formation, which means a terminator element is formed to cause translation.
Protein Data Bank (PDB)
author: Sachiyo Nomura