Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights

Lucas D. Fernandes; Alessandro P.S.De Moura; Luca Ciandrini

doi:10.1038/s41598-017-17618-1

Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights

Lucas D. Fernandes, Alessandro P.S.De Moura, Luca Ciandrini^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

11 Downloads (Pure)

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.

Original language	English
Article number	17409
Journal	Scientific Reports
Volume	7
DOIs	https://doi.org/10.1038/s41598-017-17618-1
Publication status	Published - 12 Dec 2017

Bibliographical note

The authors would like to acknowledge the funding provided by the European Union Seventh Framework Programme [FP7/2007–2013] (NICHE; grant agreement 289384) (LDF). LDF also acknowledges the funding provided by the São Paulo Research Foundation (FAPESP - grant #2015/26989-4). AM was partially funded by the UK Biotechnology and Biological Research Council (BBSRC), through grant BB/N015711/1. LC would like to acknowledge Maria Carmen Romano, Jean Hausser, Marco Cosentino Lagomarsino, Jean-Charles Walter and Norbert Kern for early discussions on this work, and the CNRS for having granted him a “demi-délégation” (2017–18). We would like to dedicate this work in memory of Maxime Clusel and Vladimir Lorman.

Keywords

biological physics
systems biology
translation

Access to Document

10.1038/s41598-017-17618-1Licence: CC BY

Gene length as a regulator for ribosome recruitment and protein synthesis theoretical insights
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Final published version, 1.57 MBLicence: CC BY
Supplementary Material: Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. https://www.nature.com/articles/s41598-017-17618-1
Final published version, 1 MBLicence: CC BY

Cite this

@article{5423f2d03dbc4da0ac524d0941d41cb3,

title = "Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights",

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.",

keywords = "biological physics, systems biology, translation",

author = "Fernandes, {Lucas D.} and Moura, {Alessandro P.S.De} and Luca Ciandrini",

note = "The authors would like to acknowledge the funding provided by the European Union Seventh Framework Programme [FP7/2007–2013] (NICHE; grant agreement 289384) (LDF). LDF also acknowledges the funding provided by the S{\~a}o Paulo Research Foundation (FAPESP - grant #2015/26989-4). AM was partially funded by the UK Biotechnology and Biological Research Council (BBSRC), through grant BB/N015711/1. LC would like to acknowledge Maria Carmen Romano, Jean Hausser, Marco Cosentino Lagomarsino, Jean-Charles Walter and Norbert Kern for early discussions on this work, and the CNRS for having granted him a “demi-d{\'e}l{\'e}gation” (2017–18). We would like to dedicate this work in memory of Maxime Clusel and Vladimir Lorman.",

year = "2017",

month = dec,

day = "12",

doi = "10.1038/s41598-017-17618-1",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Gene length as a regulator for ribosome recruitment and protein synthesis

T2 - theoretical insights

AU - Fernandes, Lucas D.

AU - Moura, Alessandro P.S.De

AU - Ciandrini, Luca

N1 - The authors would like to acknowledge the funding provided by the European Union Seventh Framework Programme [FP7/2007–2013] (NICHE; grant agreement 289384) (LDF). LDF also acknowledges the funding provided by the São Paulo Research Foundation (FAPESP - grant #2015/26989-4). AM was partially funded by the UK Biotechnology and Biological Research Council (BBSRC), through grant BB/N015711/1. LC would like to acknowledge Maria Carmen Romano, Jean Hausser, Marco Cosentino Lagomarsino, Jean-Charles Walter and Norbert Kern for early discussions on this work, and the CNRS for having granted him a “demi-délégation” (2017–18). We would like to dedicate this work in memory of Maxime Clusel and Vladimir Lorman.

PY - 2017/12/12

Y1 - 2017/12/12

N2 - 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.

AB - 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.

KW - biological physics

KW - systems biology

KW - translation

UR - http://www.scopus.com/inward/record.url?scp=85037732038&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-17618-1

DO - 10.1038/s41598-017-17618-1

M3 - Article

AN - SCOPUS:85037732038

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 17409

ER -

Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Alessandro de Moura

Cite this

Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Profiles

Alessandro de Moura

Cite this