Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1783349091282976768 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6101943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liuyubing autophagydependentribosomalrnadegradationisessentialformaintainingnucleotidehomeostasisduringcelegansdevelopment AT zouwei autophagydependentribosomalrnadegradationisessentialformaintainingnucleotidehomeostasisduringcelegansdevelopment AT yangpeiguo autophagydependentribosomalrnadegradationisessentialformaintainingnucleotidehomeostasisduringcelegansdevelopment AT wangli autophagydependentribosomalrnadegradationisessentialformaintainingnucleotidehomeostasisduringcelegansdevelopment AT mayan autophagydependentribosomalrnadegradationisessentialformaintainingnucleotidehomeostasisduringcelegansdevelopment AT zhanghong autophagydependentribosomalrnadegradationisessentialformaintainingnucleotidehomeostasisduringcelegansdevelopment AT wangxiaochen autophagydependentribosomalrnadegradationisessentialformaintainingnucleotidehomeostasisduringcelegansdevelopment |