Autophagy regulates rRNA synthesis
Autophagy has emerged as a key regulator of cell metabolism. Recently, we have demonstrated that autophagy is involved in RNA metabolism by regulating ribosomal RNA (rRNA) synthesis. We found that autophagy-deficient cells display much higher 47S precursor rRNA level, which is caused by the accumula...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Nucleus |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19491034.2022.2114661 |
| _version_ | 1798032005807472640 |
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| author | Yinfeng Xu Wei Wan |
| author_facet | Yinfeng Xu Wei Wan |
| author_sort | Yinfeng Xu |
| collection | DOAJ |
| description | Autophagy has emerged as a key regulator of cell metabolism. Recently, we have demonstrated that autophagy is involved in RNA metabolism by regulating ribosomal RNA (rRNA) synthesis. We found that autophagy-deficient cells display much higher 47S precursor rRNA level, which is caused by the accumulation of SQSTM1/p62 (sequestosome 1) but not other autophagy receptors. Mechanistically, SQSTM1 accumulation potentiates the activation of MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) signaling, which facilitates the assembly of RNA polymerase I pre-initiation complex at ribosomal DNA (rDNA) promoter regions and leads to the activation of rDNA transcription. Finally, we showed that SQSTM1 accumulation is responsible for the increase in protein synthesis, cell growth and cell proliferation in autophagy-deficient cells. Taken together, our findings reveal a regulatory role of autophagy and autophagy receptor SQSTM1 in rRNA synthesis and may provide novel mechanisms for the hyperactivated rDNA transcription in autophagy-related human diseases.Abbreviations: 5-FUrd: 5-fluorouridine; LAP: MAP1LC3/LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PIC: pre-initiation complex; POLR1: RNA polymerase I; POLR1A: RNA polymerase I subunit A; rDNA: ribosomal DNA; RRN3: RRN3 homolog, RNA polymerase I transcription factor; rRNA: ribosomal RNA; SQSTM1/p62: sequestosome 1; TP53INP2: tumor protein p53 inducible nuclear protein 2; UBTF: upstream binding transcription factor. |
| first_indexed | 2024-04-11T20:05:49Z |
| format | Article |
| id | doaj.art-5f6f443ad0c540db9b7d45d3ea6bb289 |
| institution | Directory Open Access Journal |
| issn | 1949-1034 1949-1042 |
| language | English |
| last_indexed | 2024-04-11T20:05:49Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Nucleus |
| spelling | doaj.art-5f6f443ad0c540db9b7d45d3ea6bb2892022-12-22T04:05:19ZengTaylor & Francis GroupNucleus1949-10341949-10422022-12-0113120320710.1080/19491034.2022.2114661Autophagy regulates rRNA synthesisYinfeng Xu0Wei Wan1Laboratory of Basic Biology, Hunan First Normal University, Changsha, Hunan, ChinaDepartment of Biochemistry, and Department of Thoracic Surgery of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaAutophagy has emerged as a key regulator of cell metabolism. Recently, we have demonstrated that autophagy is involved in RNA metabolism by regulating ribosomal RNA (rRNA) synthesis. We found that autophagy-deficient cells display much higher 47S precursor rRNA level, which is caused by the accumulation of SQSTM1/p62 (sequestosome 1) but not other autophagy receptors. Mechanistically, SQSTM1 accumulation potentiates the activation of MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) signaling, which facilitates the assembly of RNA polymerase I pre-initiation complex at ribosomal DNA (rDNA) promoter regions and leads to the activation of rDNA transcription. Finally, we showed that SQSTM1 accumulation is responsible for the increase in protein synthesis, cell growth and cell proliferation in autophagy-deficient cells. Taken together, our findings reveal a regulatory role of autophagy and autophagy receptor SQSTM1 in rRNA synthesis and may provide novel mechanisms for the hyperactivated rDNA transcription in autophagy-related human diseases.Abbreviations: 5-FUrd: 5-fluorouridine; LAP: MAP1LC3/LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PIC: pre-initiation complex; POLR1: RNA polymerase I; POLR1A: RNA polymerase I subunit A; rDNA: ribosomal DNA; RRN3: RRN3 homolog, RNA polymerase I transcription factor; rRNA: ribosomal RNA; SQSTM1/p62: sequestosome 1; TP53INP2: tumor protein p53 inducible nuclear protein 2; UBTF: upstream binding transcription factor.https://www.tandfonline.com/doi/10.1080/19491034.2022.2114661AutophagyMTORC1rDNArRNASQSTM1/p62 |
| spellingShingle | Yinfeng Xu Wei Wan Autophagy regulates rRNA synthesis Nucleus Autophagy MTORC1 rDNA rRNA SQSTM1/p62 |
| title | Autophagy regulates rRNA synthesis |
| title_full | Autophagy regulates rRNA synthesis |
| title_fullStr | Autophagy regulates rRNA synthesis |
| title_full_unstemmed | Autophagy regulates rRNA synthesis |
| title_short | Autophagy regulates rRNA synthesis |
| title_sort | autophagy regulates rrna synthesis |
| topic | Autophagy MTORC1 rDNA rRNA SQSTM1/p62 |
| url | https://www.tandfonline.com/doi/10.1080/19491034.2022.2114661 |
| work_keys_str_mv | AT yinfengxu autophagyregulatesrrnasynthesis AT weiwan autophagyregulatesrrnasynthesis |