Abstract
Protein synthesis rates are determined, at the translational level, by properties of the transcript’s sequence. The efficiency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or the codon usage establishing the speed of protein elongation. In this work we propose transcript length as a further key determinant of translation efficiency. Based on a physical model that considers the kinetics of ribosomes advancing on the mRNA and diffusing in its surrounding, as well as mRNA circularisation and ribosome drop-off, we explain how the transcript length may play a central role in establishing ribosome recruitment and the overall translation rate of an mRNA. According to our results, the proximity of the 3′ end to the ribosomal recruitment site of the mRNA could induce a feedback in the translation process that would favour the recycling of ribosomes. We also demonstrate how this process may be involved in shaping the experimental ribosome density-gene length dependence. Finally, we argue that cells could exploit this mechanism to adjust and balance the usage of its ribosomal resources.
Highlights
MRNA translation is, together with transcription, the pillar of the central dogma of molecular biology
MacDonald and coworkers introduced this class of model at the end of the 60′s precisely in an attempt to mathematically describe the process of mRNA translation[18]
The proximity of the 3′ end to the ribosomal recruitment site of the mRNA could induce a feedback in the translation process that would favour the translation of short transcripts over long ones, as it has been shown by experiments in the last decades
Summary
MRNA translation is, together with transcription, the pillar of the central dogma of molecular biology. A better understanding of the molecular mechanisms of mRNA translation will unravel the physiological determinants of translation efficiency This knowledge will be extremely useful in developing applications in synthetic biology and will allow tight control on the average production of a protein and on its expression noise. Many experimental observations show that the ribosome density is related to the length L of the coding sequence (CDS): the longer the mRNA, the smaller the ribosomal density This indicates the presence of a length-dependent control of translation. The common traits in the density-length dependence suggest that this relationship is dictated by universal mechanisms underlying the translation process This remark has been strangely overlooked in the literature (with the exception of Guo et al.16), in the theoretical literature trying to provide models of mRNA translation. In contrast with previous studies, here we explain qualitatively and quantitatively the relationship between ribosome density and CDS length, making the point that transcript length is a critical determinant of protein synthesis rates
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