Cellular stress and nucleolar function
Open accessAbstract
All organisms sense and respond to conditions that stress their homeostatic mechanisms. Here we review current studies showing that the nucleolus, long regarded as a mere ribosome producing factory, plays a key role in monitoring and responding to cellular stress. After exposure to extra- or intracellular stress, cells rapidly down-regulate the synthesis of ribosomal RNA. Impairment of nucleolar function in response to stress is accompanied by perturbation of nucleolar structure, cell cycle arrest and stabilization of p53. The nucleolar target for down-regulation of rDNA transcription is TIF-IA, an essential transcription factor that modulates the activity of RNA polymerase I (Pol I). Upon stress, TIF-IA is phosphorylated by c-Jun N-terminal kinase 2 (JNK2). Phosphorylation prevents TIF-IA from interaction with Pol I, thereby impairing transcription complex formation and rRNA synthesis. Furthermore, stress-induced inactivation of TIF-IA is accompanied by translocation of TIF-IA from the nucleolus to the nucleoplasm. These findings, together with other data showing stress-induced release of nucleolar proteins to carry out other regulatory functions, reinforce the growing realization that nucleoli orchestrate the chain of events the cell uses to properly respond to stress signals.
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miRNAs capable of repressing transcripts encoding ribosomal proteins could indirectly constrain ribosome biogenesis.
“Because ribosome assembly depends on the coordinated production of ribosomal proteins in the cytoplasm, miRNAs capable of repressing transcripts encoding these proteins could indirectly constrain ribosome biogenesis [194].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [194]
In “The Nucleolus—Classical and Novel Functions” (page not provided), the paper says ribosomal proteins associate with rRNAs during ribosome assembly, supporting the premise that those proteins are needed. It does not discuss miRNAs repressing ribosomal-protein transcripts or say that such repression constrains ribosome biogenesis. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSeveral classes of non-coding RNAs, including lncRNAs, miRNAs, and snoRNAs, participate in the control of nucleolar activity and ribosome production.
“Increasing evidence indicates that several classes of non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNAs), participate in the control of nucleolar activity and ribosome production [194,195].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [194]
The section “The Nucleolus—Classical and Novel Functions” (page unavailable) describes rRNA processing and ribosome assembly, while “JNK2 Downregulates rRNA Synthesis Under Stress” (page unavailable) discusses protein-mediated control of rRNA synthesis. Searches for non-coding RNAs, lncRNAs, miRNAs, and snoRNAs found no passage linking those RNA classes to control of nucleolar activity or ribosome production. (LLM, conf=0.72)
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Cites
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Flagged first, then by citations
Research works printed but not linked: 2
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“Because ribosome assembly depends on the coordinated production of ribosomal proteins in the cytoplasm, miRNAs capable of repressing transcripts encoding these proteins could indirectly constrain ribosome biogenesis [194].”
- Authors
- Mayer, C., & Grummt, I.
- Affiliations
- German Cancer Research Center (DE)
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2005-05-13
- Volume
- 4
- Issue
- 8
- Pages
- 1036-1038
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2093549030
- Cited by
- 233
- References
- 17
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 5 · 2019: 10 · 2018: 13 · 2017: 12 · 2016: 11 · 2015: 15 · 2014: 10 · 2013: 21 · 2012: 15
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- nucleolus, cellular stress response, rDNA transcription, TIF-IA, RNA polymerase I, p53 stabilization, cell cycle arrest, nucleolar structure, homeostasis
- MeSH terms
- Animals, Cell Cycle, Cell Nucleolus, Cell Nucleus, DNA, Ribosomal, Guanosine Triphosphate, Humans, Microscopy, Fluorescence, Phosphorylation, Protein Binding, RNA, RNA, Ribosomal, Transcription Factors, Transcription, Genetic, Down-Regulation, Tumor Suppressor Protein p53, Protein Transport, NIH 3T3 Cells, JNK Mitogen-Activated Protein Kinases, Cell Proliferation, Mice
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