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Landscape of the complete RNA chemical modifications in the human 80S ribosome

During ribosome biogenesis, ribosomal RNAs acquire various chemical modifications that ensure the fidelity of translation, and dysregulation of the modification processes can cause proteome changes as observed in cancer and inherited human disorders. Here, we report the complete chemical modificatio...

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Autores principales: Taoka, Masato, Nobe, Yuko, Yamaki, Yuka, Sato, Ko, Ishikawa, Hideaki, Izumikawa, Keiichi, Yamauchi, Yoshio, Hirota, Kouji, Nakayama, Hiroshi, Takahashi, Nobuhiro, Isobe, Toshiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182160/
https://www.ncbi.nlm.nih.gov/pubmed/30202881
http://dx.doi.org/10.1093/nar/gky811
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author Taoka, Masato
Nobe, Yuko
Yamaki, Yuka
Sato, Ko
Ishikawa, Hideaki
Izumikawa, Keiichi
Yamauchi, Yoshio
Hirota, Kouji
Nakayama, Hiroshi
Takahashi, Nobuhiro
Isobe, Toshiaki
author_facet Taoka, Masato
Nobe, Yuko
Yamaki, Yuka
Sato, Ko
Ishikawa, Hideaki
Izumikawa, Keiichi
Yamauchi, Yoshio
Hirota, Kouji
Nakayama, Hiroshi
Takahashi, Nobuhiro
Isobe, Toshiaki
author_sort Taoka, Masato
collection PubMed
description During ribosome biogenesis, ribosomal RNAs acquire various chemical modifications that ensure the fidelity of translation, and dysregulation of the modification processes can cause proteome changes as observed in cancer and inherited human disorders. Here, we report the complete chemical modifications of all RNAs of the human 80S ribosome as determined with quantitative mass spectrometry. We assigned 228 sites with 14 different post-transcriptional modifications, most of which are located in functional regions of the ribosome. All modifications detected are typical of eukaryotic ribosomal RNAs, and no human-specific modifications were observed, in contrast to a recently reported cryo-electron microscopy analysis. While human ribosomal RNAs appeared to have little polymorphism regarding the post-transcriptional modifications, we found that pseudouridylation at two specific sites in 28S ribosomal RNA are significantly reduced in ribosomes of patients with familial dyskeratosis congenita, a genetic disease caused by a point mutation in the pseudouridine synthase gene DKC1. The landscape of the entire epitranscriptomic ribosomal RNA modifications provides a firm basis for understanding ribosome function and dysfunction associated with human disease.
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spelling pubmed-61821602018-10-18 Landscape of the complete RNA chemical modifications in the human 80S ribosome Taoka, Masato Nobe, Yuko Yamaki, Yuka Sato, Ko Ishikawa, Hideaki Izumikawa, Keiichi Yamauchi, Yoshio Hirota, Kouji Nakayama, Hiroshi Takahashi, Nobuhiro Isobe, Toshiaki Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry During ribosome biogenesis, ribosomal RNAs acquire various chemical modifications that ensure the fidelity of translation, and dysregulation of the modification processes can cause proteome changes as observed in cancer and inherited human disorders. Here, we report the complete chemical modifications of all RNAs of the human 80S ribosome as determined with quantitative mass spectrometry. We assigned 228 sites with 14 different post-transcriptional modifications, most of which are located in functional regions of the ribosome. All modifications detected are typical of eukaryotic ribosomal RNAs, and no human-specific modifications were observed, in contrast to a recently reported cryo-electron microscopy analysis. While human ribosomal RNAs appeared to have little polymorphism regarding the post-transcriptional modifications, we found that pseudouridylation at two specific sites in 28S ribosomal RNA are significantly reduced in ribosomes of patients with familial dyskeratosis congenita, a genetic disease caused by a point mutation in the pseudouridine synthase gene DKC1. The landscape of the entire epitranscriptomic ribosomal RNA modifications provides a firm basis for understanding ribosome function and dysfunction associated with human disease. Oxford University Press 2018-10-12 2018-09-07 /pmc/articles/PMC6182160/ /pubmed/30202881 http://dx.doi.org/10.1093/nar/gky811 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemical Biology and Nucleic Acid Chemistry
Taoka, Masato
Nobe, Yuko
Yamaki, Yuka
Sato, Ko
Ishikawa, Hideaki
Izumikawa, Keiichi
Yamauchi, Yoshio
Hirota, Kouji
Nakayama, Hiroshi
Takahashi, Nobuhiro
Isobe, Toshiaki
Landscape of the complete RNA chemical modifications in the human 80S ribosome
title Landscape of the complete RNA chemical modifications in the human 80S ribosome
title_full Landscape of the complete RNA chemical modifications in the human 80S ribosome
title_fullStr Landscape of the complete RNA chemical modifications in the human 80S ribosome
title_full_unstemmed Landscape of the complete RNA chemical modifications in the human 80S ribosome
title_short Landscape of the complete RNA chemical modifications in the human 80S ribosome
title_sort landscape of the complete rna chemical modifications in the human 80s ribosome
topic Chemical Biology and Nucleic Acid Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182160/
https://www.ncbi.nlm.nih.gov/pubmed/30202881
http://dx.doi.org/10.1093/nar/gky811
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