ArticleNucleic acids research2014
Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
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- Small Nucleolar RNAs and Their Comprehensive Biological Functions in Hepatocellular Carcinoma.Cells · 2022Review
- Rapamycin-filgrastim combination therapy ameliorates portal hypertension-induced splenomegaly: Role of β actin and S100A9 proteins modulation.Iranian journal of basic medical sciences · 2022Article
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- Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis.Nature communications · 2021Article
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- BOP1 Silencing Suppresses Gastric Cancer Proliferation through p53 Modulation.Current medical science · 2021Article
- Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.Frontiers in molecular biosciences · 2021Review
- BOP1 Knockdown Attenuates Neointimal Hyperplasia by Activating p53 and Inhibiting Nascent Protein Synthesis.Oxidative medicine and cellular longevity · 2021Article
- BOP1 Used as a Novel Prognostic Marker and Correlated with Tumor Microenvironment in Pan-Cancer.Journal of oncology · 2021Article
- Disabling MNK protein kinases promotes oxidative metabolism and protects against diet-induced obesity.Molecular metabolism · 2020Article
- Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins.Nucleic acids research · 2020Article
- Cockayne syndrome group A and B proteins function in rRNA transcription through nucleolin regulation.Nucleic acids research · 2020Article
- Ribosome queuing enables non-AUG translation to be resistant to multiple protein synthesis inhibitors.Genes & development · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ribosome biogenesis is a key process for maintaining protein synthetic capacity in dividing or growing cells, and requires coordinated production of ribosomal proteins and ribosomal RNA (rRNA), including the processing of the latter. Signalling through mammalian target of rapamycin complex 1 (mTORC1) activates all these processes. Here, we show that, in human cells, impaired rRNA processing, caused by expressing an interfering mutant of BOP1 or by knocking down components of the PeBoW complex elicits activation of mTORC1 signalling. This leads to enhanced phosphorylation of its substrates S6K1 and 4E-BP1, and stimulation of proteins involved in translation initiation and elongation. In particular, we observe both inactivation and downregulation of the eukaryotic elongation factor 2 kinase, which normally inhibits translation elongation. The latter effect involves decreased expression of the eEF2K mRNA. The mRNAs for ribosomal proteins, whose translation is positively regulated by mTORC1 signalling, also remain associated with ribosomes. Therefore, our data demonstrate that disrupting rRNA production activates mTORC1 signalling to enhance the efficiency of the translational machinery, likely to help compensate for impaired ribosome production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.