Experiments that can potentially test the hypothesized physical mechanisms are discussed. If cooperative interactions among the loop-promoting proteins and the initiation/termination sites are considered, the throughput can be further regulated in a nonmonotonic manner. We find that the initiation, or initial ribosome adsorption binding required for maximal throughput, can vary dramatically depending on certain values of the bulk ribosome concentration and diffusion constant. The probability distribution of the distance between the initiation and termination sites is described using simple noninteracting polymer models. Additional mRNA binding factors can also promote loop formation, or cyclization, bringing the initiation and termination sites into close proximity. Since the ribosome injection rates of the totally asymmetric exclusion process depend on the local concentrations at the initiation site, a source of ribosomes emanating from the termination end can feed back to the initiation site, leading to a self-consistent set of equations for the steady-state ribosome throughput. The elongation steps of the mRNA-bound ribosomes are modeled using exact and asymptotic results of the totally asymmetric exclusion process. After elongation and detachment from the 3′ termination site of mRNA, parts of the ribosome machinery can diffuse back to the initiation site, especially if it is held nearby, enhancing overall translation rates.
We explore and quantify the physical and biochemical mechanisms that may be relevant in the regulation of translation.
0 kommentar(er)
