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Visualizing formation of the active site in the mitochondrial ribosome
Ribosome assembly is an essential and conserved process that is regulated at each step by specific factors. Using cryo-electron microscopy (cryo-EM), we visualize the formation of the conserved peptidyl transferase center (PTC) of the human mitochondrial ribosome. The conserved GTPase GTPBP7 regulat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492066/ https://www.ncbi.nlm.nih.gov/pubmed/34609277 http://dx.doi.org/10.7554/eLife.68806 |
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author | Chandrasekaran, Viswanathan Desai, Nirupa Burton, Nicholas O Yang, Hanting Price, Jon Miska, Eric A Ramakrishnan, V |
author_facet | Chandrasekaran, Viswanathan Desai, Nirupa Burton, Nicholas O Yang, Hanting Price, Jon Miska, Eric A Ramakrishnan, V |
author_sort | Chandrasekaran, Viswanathan |
collection | PubMed |
description | Ribosome assembly is an essential and conserved process that is regulated at each step by specific factors. Using cryo-electron microscopy (cryo-EM), we visualize the formation of the conserved peptidyl transferase center (PTC) of the human mitochondrial ribosome. The conserved GTPase GTPBP7 regulates the correct folding of 16S ribosomal RNA (rRNA) helices and ensures 2ʹ-O-methylation of the PTC base U3039. GTPBP7 binds the RNA methyltransferase NSUN4 and MTERF4, which sequester H68-71 of the 16S rRNA and allow biogenesis factors to access the maturing PTC. Mutations that disrupt binding of their Caenorhabditis elegans orthologs to the large subunit potently activate mitochondrial stress and cause viability, development, and sterility defects. Next-generation RNA sequencing reveals widespread gene expression changes in these mutant animals that are indicative of mitochondrial stress response activation. We also answer the long-standing question of why NSUN4, but not its enzymatic activity, is indispensable for mitochondrial protein synthesis. |
format | Online Article Text |
id | pubmed-8492066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-84920662021-10-06 Visualizing formation of the active site in the mitochondrial ribosome Chandrasekaran, Viswanathan Desai, Nirupa Burton, Nicholas O Yang, Hanting Price, Jon Miska, Eric A Ramakrishnan, V eLife Biochemistry and Chemical Biology Ribosome assembly is an essential and conserved process that is regulated at each step by specific factors. Using cryo-electron microscopy (cryo-EM), we visualize the formation of the conserved peptidyl transferase center (PTC) of the human mitochondrial ribosome. The conserved GTPase GTPBP7 regulates the correct folding of 16S ribosomal RNA (rRNA) helices and ensures 2ʹ-O-methylation of the PTC base U3039. GTPBP7 binds the RNA methyltransferase NSUN4 and MTERF4, which sequester H68-71 of the 16S rRNA and allow biogenesis factors to access the maturing PTC. Mutations that disrupt binding of their Caenorhabditis elegans orthologs to the large subunit potently activate mitochondrial stress and cause viability, development, and sterility defects. Next-generation RNA sequencing reveals widespread gene expression changes in these mutant animals that are indicative of mitochondrial stress response activation. We also answer the long-standing question of why NSUN4, but not its enzymatic activity, is indispensable for mitochondrial protein synthesis. eLife Sciences Publications, Ltd 2021-10-05 /pmc/articles/PMC8492066/ /pubmed/34609277 http://dx.doi.org/10.7554/eLife.68806 Text en © 2021, Chandrasekaran et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Chandrasekaran, Viswanathan Desai, Nirupa Burton, Nicholas O Yang, Hanting Price, Jon Miska, Eric A Ramakrishnan, V Visualizing formation of the active site in the mitochondrial ribosome |
title | Visualizing formation of the active site in the mitochondrial ribosome |
title_full | Visualizing formation of the active site in the mitochondrial ribosome |
title_fullStr | Visualizing formation of the active site in the mitochondrial ribosome |
title_full_unstemmed | Visualizing formation of the active site in the mitochondrial ribosome |
title_short | Visualizing formation of the active site in the mitochondrial ribosome |
title_sort | visualizing formation of the active site in the mitochondrial ribosome |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492066/ https://www.ncbi.nlm.nih.gov/pubmed/34609277 http://dx.doi.org/10.7554/eLife.68806 |
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