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Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development

Ribosome degradation through the autophagy-lysosome pathway is crucial for cell survival during nutrient starvation, but whether it occurs under normal growth conditions and contributes to animal physiology remains unaddressed. In this study, we identified RNST-2, a C. elegans T2 family endoribonucl...

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Autores principales: Liu, Yubing, Zou, Wei, Yang, Peiguo, Wang, Li, Ma, Yan, Zhang, Hong, Wang, Xiaochen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101943/
https://www.ncbi.nlm.nih.gov/pubmed/30102152
http://dx.doi.org/10.7554/eLife.36588
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author Liu, Yubing
Zou, Wei
Yang, Peiguo
Wang, Li
Ma, Yan
Zhang, Hong
Wang, Xiaochen
author_facet Liu, Yubing
Zou, Wei
Yang, Peiguo
Wang, Li
Ma, Yan
Zhang, Hong
Wang, Xiaochen
author_sort Liu, Yubing
collection PubMed
description Ribosome degradation through the autophagy-lysosome pathway is crucial for cell survival during nutrient starvation, but whether it occurs under normal growth conditions and contributes to animal physiology remains unaddressed. In this study, we identified RNST-2, a C. elegans T2 family endoribonuclease, as the key enzyme that degrades ribosomal RNA in lysosomes. We found that loss of rnst-2 causes accumulation of rRNA and ribosomal proteins in enlarged lysosomes and both phenotypes are suppressed by blocking autophagy, which indicates that RNST-2 mediates autophagic degradation of ribosomal RNA in lysosomes. rnst-2(lf) mutants are defective in embryonic and larval development and are short-lived. Remarkably, simultaneous loss of RNST-2 and de novo synthesis of pyrimidine nucleotides leads to complete embryonic lethality, which is suppressed by supplements of uridine or cytidine. Our study reveals an essential role of autophagy-dependent degradation of ribosomal RNA in maintaining nucleotide homeostasis during animal development.
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spelling pubmed-61019432018-08-22 Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development Liu, Yubing Zou, Wei Yang, Peiguo Wang, Li Ma, Yan Zhang, Hong Wang, Xiaochen eLife Cell Biology Ribosome degradation through the autophagy-lysosome pathway is crucial for cell survival during nutrient starvation, but whether it occurs under normal growth conditions and contributes to animal physiology remains unaddressed. In this study, we identified RNST-2, a C. elegans T2 family endoribonuclease, as the key enzyme that degrades ribosomal RNA in lysosomes. We found that loss of rnst-2 causes accumulation of rRNA and ribosomal proteins in enlarged lysosomes and both phenotypes are suppressed by blocking autophagy, which indicates that RNST-2 mediates autophagic degradation of ribosomal RNA in lysosomes. rnst-2(lf) mutants are defective in embryonic and larval development and are short-lived. Remarkably, simultaneous loss of RNST-2 and de novo synthesis of pyrimidine nucleotides leads to complete embryonic lethality, which is suppressed by supplements of uridine or cytidine. Our study reveals an essential role of autophagy-dependent degradation of ribosomal RNA in maintaining nucleotide homeostasis during animal development. eLife Sciences Publications, Ltd 2018-08-13 /pmc/articles/PMC6101943/ /pubmed/30102152 http://dx.doi.org/10.7554/eLife.36588 Text en © 2018, Liu et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Liu, Yubing
Zou, Wei
Yang, Peiguo
Wang, Li
Ma, Yan
Zhang, Hong
Wang, Xiaochen
Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
title Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
title_full Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
title_fullStr Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
title_full_unstemmed Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
title_short Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
title_sort autophagy-dependent ribosomal rna degradation is essential for maintaining nucleotide homeostasis during c. elegans development
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101943/
https://www.ncbi.nlm.nih.gov/pubmed/30102152
http://dx.doi.org/10.7554/eLife.36588
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