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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/36588 |
| _version_ | 1811199380912340992 |
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| author | Yubing Liu Wei Zou Peiguo Yang Li Wang Yan Ma Hong Zhang Xiaochen Wang |
| author_facet | Yubing Liu Wei Zou Peiguo Yang Li Wang Yan Ma Hong Zhang Xiaochen Wang |
| author_sort | Yubing Liu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T01:47:22Z |
| format | Article |
| id | doaj.art-70abfc792d104018821d3a329c64739c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:47:22Z |
| publishDate | 2018-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-70abfc792d104018821d3a329c64739c2022-12-22T03:53:02ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.36588Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans developmentYubing Liu0Wei Zou1Peiguo Yang2Li Wang3Yan Ma4Hong Zhang5Xiaochen Wang6https://orcid.org/0000-0002-4344-0925Peking University-Tsinghua University-National Institute of Biological Joint Graduate Program, School of Life Sciences, Peking University, Beijing, China; National Institute of Biological Science, Beijing, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaNational Institute of Biological Science, Beijing, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaNational Institute of Biological Science, Beijing, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaRibosome 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.https://elifesciences.org/articles/36588lysosomeautophagydevelopment |
| spellingShingle | Yubing Liu Wei Zou Peiguo Yang Li Wang Yan Ma Hong Zhang Xiaochen Wang Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development eLife lysosome autophagy 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 | lysosome autophagy development |
| url | https://elifesciences.org/articles/36588 |
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