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The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner.
Nucleic Acids Res. 2017 Nov 16; 45(20):11725-11742.NA

Abstract

The nuclear mitotic apparatus protein, NuMA, is involved in major cellular events such as DNA damage response, apoptosis and p53-mediated growth-arrest, all of which are under the control of the nucleolus upon stress. Proteomic investigation has identified NuMA among hundreds of nucleolar proteins. Yet, the precise link between NuMA and nucleolar function remains undetermined. We confirm that NuMA is present in the nucleolus and reveal redistribution of NuMA upon actinomycin D or doxorubicin-induced nucleolar stress. NuMA coimmunoprecipitates with RNA polymerase I, with ribosomal proteins RPL26 and RPL24, and with components of B-WICH, an ATP-dependent chromatin remodeling complex associated with rDNA transcription. NuMA also binds to 18S and 28S rRNAs and localizes to rDNA promoter regions. Downregulation of NuMA expression triggers nucleolar stress, as shown by decreased nascent pre-rRNA synthesis, fibrillarin perinucleolar cap formation and upregulation of p27kip1, but not p53. Physiologically relevant nucleolar stress induction with reactive oxygen species reaffirms a p53-independent p27kip1 response pathway and leads to nascent pre-rRNA reduction. It also promotes the decrease in the amount of NuMA. This previously uncharacterized function of NuMA in rDNA transcription and p53-independent nucleolar stress response supports a central role for this nuclear structural protein in cellular homeostasis.

Authors+Show Affiliations

Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-2026, USA. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-2026, USA.Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-2026, USA.Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-2026, USA.Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-2026, USA.Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-2026, USA.Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-2026, USA. Center for Cancer Research, Purdue University, West Lafayette, IN 47907-2026, USA.Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-2026, USA. Center for Cancer Research, Purdue University, West Lafayette, IN 47907-2026, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28981686

Citation

Jayaraman, Swaathi, et al. "The Nuclear Mitotic Apparatus Protein NuMA Controls rDNA Transcription and Mediates the Nucleolar Stress Response in a P53-independent Manner." Nucleic Acids Research, vol. 45, no. 20, 2017, pp. 11725-11742.
Jayaraman S, Chittiboyina S, Bai Y, et al. The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner. Nucleic Acids Res. 2017;45(20):11725-11742.
Jayaraman, S., Chittiboyina, S., Bai, Y., Abad, P. C., Vidi, P. A., Stauffacher, C. V., & Lelièvre, S. A. (2017). The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner. Nucleic Acids Research, 45(20), 11725-11742. https://doi.org/10.1093/nar/gkx782
Jayaraman S, et al. The Nuclear Mitotic Apparatus Protein NuMA Controls rDNA Transcription and Mediates the Nucleolar Stress Response in a P53-independent Manner. Nucleic Acids Res. 2017 Nov 16;45(20):11725-11742. PubMed PMID: 28981686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner. AU - Jayaraman,Swaathi, AU - Chittiboyina,Shirisha, AU - Bai,Yunfeng, AU - Abad,Patricia C, AU - Vidi,Pierre-Alexandre, AU - Stauffacher,Cynthia V, AU - Lelièvre,Sophie A, PY - 2017/03/28/received PY - 2017/08/30/accepted PY - 2017/10/6/pubmed PY - 2017/12/13/medline PY - 2017/10/6/entrez SP - 11725 EP - 11742 JF - Nucleic acids research JO - Nucleic Acids Res. VL - 45 IS - 20 N2 - The nuclear mitotic apparatus protein, NuMA, is involved in major cellular events such as DNA damage response, apoptosis and p53-mediated growth-arrest, all of which are under the control of the nucleolus upon stress. Proteomic investigation has identified NuMA among hundreds of nucleolar proteins. Yet, the precise link between NuMA and nucleolar function remains undetermined. We confirm that NuMA is present in the nucleolus and reveal redistribution of NuMA upon actinomycin D or doxorubicin-induced nucleolar stress. NuMA coimmunoprecipitates with RNA polymerase I, with ribosomal proteins RPL26 and RPL24, and with components of B-WICH, an ATP-dependent chromatin remodeling complex associated with rDNA transcription. NuMA also binds to 18S and 28S rRNAs and localizes to rDNA promoter regions. Downregulation of NuMA expression triggers nucleolar stress, as shown by decreased nascent pre-rRNA synthesis, fibrillarin perinucleolar cap formation and upregulation of p27kip1, but not p53. Physiologically relevant nucleolar stress induction with reactive oxygen species reaffirms a p53-independent p27kip1 response pathway and leads to nascent pre-rRNA reduction. It also promotes the decrease in the amount of NuMA. This previously uncharacterized function of NuMA in rDNA transcription and p53-independent nucleolar stress response supports a central role for this nuclear structural protein in cellular homeostasis. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/28981686/The_nuclear_mitotic_apparatus_protein_NuMA_controls_rDNA_transcription_and_mediates_the_nucleolar_stress_response_in_a_p53_independent_manner_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx782 DB - PRIME DP - Unbound Medicine ER -