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The Nucleolus as a Stress Response Organelle

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Proteins of the Nucleolus

Abstract

The nucleolus reacts to several forms of cellular stress, which disturb the normal nucleolar functions in ribosomal DNA (rDNA) transcription and ribosome assembly. These include agents that inhibit transcription by RNA polymerase I -complex, e.g. DNA damage or cytotoxic drugs. These cause so called “ribosomal stress” or “nucleolar stress” involving nucleolar disruption and induction of a stress response with tumor suppressor p53 and its negative regulator MDM2 as the key players. On the other hand, proteotoxic stress induced by e.g. hampered protein degradation due to proteasome inhibition or increased protein synthesis due to a viral infection, can cause formation of insoluble protein and RNA aggregates to nucleoli. These nucleolar aggresomes may reflect the connections of nucleoli in nuclear export of proteins and RNA. In addition, the nucleolus is central in the regulation of certain tumor suppressor and oncogene activities. The importance of these cellular processes and nucleolar stress responses are underscored in major diseases like cancer, ribosomopathies, and even inclusion diseases. In this chapter, we introduce the nucleolus as a stress-responsive organelle, and discuss the connections with human disease.

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Abbreviations

Act D:

Actinomycin D

DBA:

Diamond Blackfan anemia

DFC:

Dense fibrillar component

FC:

Fibrillar center

GC:

Granular component

HD:

Huntington’s disease

Mdm2:

Mouse double minute 2

OPMD:

Oculopharyngeal muscular dystrophy

poly(A) RNA:

Polyadenylated RNA

polyQ:

Polyglutamine

rDNA:

Ribosomal DNA

RNA pol:

RNA polymerase

rRNA:

Ribosomal RNA

SCA:

Spinocerebellar ataxia

UPS:

Ubiquitin proteasome system

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Acknowledgements

The original work of LL related to this subject was supported by the Finnish Academy (grant no. 108828). Prof. Tapio Visakorpi for his kind support to LL. Research on the nucleolus and ribosomal proteins in the ML project group is supported by the Swedish Research Council, project number K2012-99X-2969-01-3, and the Karolinska Institutet.

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  1. Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, 17176, Sweden

    Mikael S. Lindström

  2. Institute of Biomedical Technology and BioMediTech, University of Tampere, Tampere, 33014, Finland

    Leena Latonen

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  1. Mikael S. Lindström
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  2. Leena Latonen
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Correspondence to Leena Latonen .

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  1. , Biology, University of Toronto at Mississauga, Mississauga Rd. N. 3359, Mississauga, L5L1C6, Ontario, Canada

    Danton H O'Day

  2. , Biology, University of Toronto at Mississauga, Mississauga Rd. 3359, Mississauga, L5L1C6, Ontario, Canada

    Andrew Catalano

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Lindström, M.S., Latonen, L. (2013). The Nucleolus as a Stress Response Organelle. In: O'Day, D., Catalano, A. (eds) Proteins of the Nucleolus. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5818-6_11

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