The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.

Previous studies have shown that translation elongation is regulated by multiple factors, but the observed heterogeneity remains only partially explained. To dissect quantitatively the different determinants of elongation speed, we use probabilistic modeling to estimate initiation and local elongati...

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Main Authors: Khanh Dao Duc, Yun S Song
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC5786338?pdf=render
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author Khanh Dao Duc
Yun S Song
author_facet Khanh Dao Duc
Yun S Song
author_sort Khanh Dao Duc
collection DOAJ
description Previous studies have shown that translation elongation is regulated by multiple factors, but the observed heterogeneity remains only partially explained. To dissect quantitatively the different determinants of elongation speed, we use probabilistic modeling to estimate initiation and local elongation rates from ribosome profiling data. This model-based approach allows us to quantify the extent of interference between ribosomes on the same transcript. We show that neither interference nor the distribution of slow codons is sufficient to explain the observed heterogeneity. Instead, we find that electrostatic interactions between the ribosomal exit tunnel and specific parts of the nascent polypeptide govern the elongation rate variation as the polypeptide makes its initial pass through the tunnel. Once the N-terminus has escaped the tunnel, the hydropathy of the nascent polypeptide within the ribosome plays a major role in modulating the speed. We show that our results are consistent with the biophysical properties of the tunnel.
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spelling doaj.art-fe92e74a3e6a480ebbd197a9047abdde2022-12-21T21:47:01ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-01-01141e100716610.1371/journal.pgen.1007166The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.Khanh Dao DucYun S SongPrevious studies have shown that translation elongation is regulated by multiple factors, but the observed heterogeneity remains only partially explained. To dissect quantitatively the different determinants of elongation speed, we use probabilistic modeling to estimate initiation and local elongation rates from ribosome profiling data. This model-based approach allows us to quantify the extent of interference between ribosomes on the same transcript. We show that neither interference nor the distribution of slow codons is sufficient to explain the observed heterogeneity. Instead, we find that electrostatic interactions between the ribosomal exit tunnel and specific parts of the nascent polypeptide govern the elongation rate variation as the polypeptide makes its initial pass through the tunnel. Once the N-terminus has escaped the tunnel, the hydropathy of the nascent polypeptide within the ribosome plays a major role in modulating the speed. We show that our results are consistent with the biophysical properties of the tunnel.http://europepmc.org/articles/PMC5786338?pdf=render
spellingShingle Khanh Dao Duc
Yun S Song
The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.
PLoS Genetics
title The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.
title_full The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.
title_fullStr The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.
title_full_unstemmed The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.
title_short The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.
title_sort impact of ribosomal interference codon usage and exit tunnel interactions on translation elongation rate variation
url http://europepmc.org/articles/PMC5786338?pdf=render
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