Ribosome recycling, diffusion, and mRNA loop formation in translational regulation

TL;DR

This paper investigates how physical diffusion, mRNA looping, and biochemical feedback mechanisms influence translation regulation, modeling ribosome dynamics and mRNA structure to understand their combined effects on translation efficiency.

Contribution

It introduces a comprehensive model combining ribosome diffusion, mRNA looping, and feedback to explain translation regulation mechanisms.

Findings

Ribosome diffusion back to initiation enhances translation rates.

mRNA loop formation can regulate ribosome throughput.

Ribosome concentration and diffusion constants critically affect initiation.

Abstract

We explore and quantify the physical and biochemical mechanisms that may be relevant in the regulation of translation. 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. The elongation steps of the mRNA-bound ribosomes are modeled using exact and asymptotic results of the totally asymmetric exclusion process (TASEP).Since the ribosome injection rates of the TASEP 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. Additional mRNA binding factors can also promote loop formation, or cyclization, bringing the initiation and termination sites into close proximity. The probability distribution of the distance between the initiation and termination sites is described using simple noninteracting polymer models. 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. 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. Potential experiments to test the hypothesized physical mechanisms are discussed.