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Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A

The quickly accumulating ribosome profiling data is an insightful resource for studying the critical details of translation regulation under various biological contexts. Rocaglamide A (RocA), an antitumor heterotricyclic natural compound, has been shown to inhibit translation initiation of a large g...

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Autores principales: Li, Fajin, Fang, Jianhuo, Yu, Yifan, Hao, Sijia, Zou, Qin, Zeng, Qinglin, Yang, Xuerui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891901/
https://www.ncbi.nlm.nih.gov/pubmed/36725859
http://dx.doi.org/10.1038/s41467-023-36290-w
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author Li, Fajin
Fang, Jianhuo
Yu, Yifan
Hao, Sijia
Zou, Qin
Zeng, Qinglin
Yang, Xuerui
author_facet Li, Fajin
Fang, Jianhuo
Yu, Yifan
Hao, Sijia
Zou, Qin
Zeng, Qinglin
Yang, Xuerui
author_sort Li, Fajin
collection PubMed
description The quickly accumulating ribosome profiling data is an insightful resource for studying the critical details of translation regulation under various biological contexts. Rocaglamide A (RocA), an antitumor heterotricyclic natural compound, has been shown to inhibit translation initiation of a large group of mRNA species by clamping eIF4A onto poly-purine motifs in the 5′ UTRs. However, reanalysis of previous ribosome profiling datasets reveals an unexpected shift of the ribosome occupancy pattern, upon RocA treatment in various types of cells, during early translation elongation for a specific group of mRNA transcripts without poly-purine motifs over-represented in their 5′ UTRs. Such perturbation of translation elongation dynamics can be attributed to the blockage of translating ribosomes due to the binding of eIF4A to the poly-purine sequence in coding regions. In summary, our study presents the complete dual modes of RocA in blocking translation initiation and elongation, which underlie the potent antitumor effect of RocA.
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spelling pubmed-98919012023-02-02 Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A Li, Fajin Fang, Jianhuo Yu, Yifan Hao, Sijia Zou, Qin Zeng, Qinglin Yang, Xuerui Nat Commun Article The quickly accumulating ribosome profiling data is an insightful resource for studying the critical details of translation regulation under various biological contexts. Rocaglamide A (RocA), an antitumor heterotricyclic natural compound, has been shown to inhibit translation initiation of a large group of mRNA species by clamping eIF4A onto poly-purine motifs in the 5′ UTRs. However, reanalysis of previous ribosome profiling datasets reveals an unexpected shift of the ribosome occupancy pattern, upon RocA treatment in various types of cells, during early translation elongation for a specific group of mRNA transcripts without poly-purine motifs over-represented in their 5′ UTRs. Such perturbation of translation elongation dynamics can be attributed to the blockage of translating ribosomes due to the binding of eIF4A to the poly-purine sequence in coding regions. In summary, our study presents the complete dual modes of RocA in blocking translation initiation and elongation, which underlie the potent antitumor effect of RocA. Nature Publishing Group UK 2023-02-02 /pmc/articles/PMC9891901/ /pubmed/36725859 http://dx.doi.org/10.1038/s41467-023-36290-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access 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://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Fajin
Fang, Jianhuo
Yu, Yifan
Hao, Sijia
Zou, Qin
Zeng, Qinglin
Yang, Xuerui
Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
title Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
title_full Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
title_fullStr Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
title_full_unstemmed Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
title_short Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
title_sort reanalysis of ribosome profiling datasets reveals a function of rocaglamide a in perturbing the dynamics of translation elongation via eif4a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891901/
https://www.ncbi.nlm.nih.gov/pubmed/36725859
http://dx.doi.org/10.1038/s41467-023-36290-w
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