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Ectopically expressed pNO40 suppresses ribosomal RNA synthesis by inhibiting UBF-dependent transcription activation.
Biochem Biophys Res Commun 2019; 516(2):381-387BB

Abstract

Ribosomal RNA (rRNA) production occurs in the nucleolus and is a critical process for ribosome biogenesis which affects protein synthesis capacity and determines the cell growth. Dysregulation of nucleolar homeostasis elicits a nucleolar stress response and is related to disease etiology, indicating that the regulation of nucleolar activity is crucial and tightly coordinated. We previously reported that nucleolar protein pNO40 overexpression mediates SR family splicing factors into the nucleolus and impairs mRNA metabolism, while the function of pNO40 in nucleolar homeostasis is unclear. Here, we demonstrate that overexpression of pNO40 downregulates RNA polymerase I transcription activity, resulting in pre-rRNA synthesis reduction and induces nucleolar segregation, a hallmark of rRNA synthesis inhibition and nucleolar stress response. Moreover, co-immunoprecipitation experiments revealed that ectopically expressed pNO40 interacts with UBF, a master transcription factor involved in pre-initiation complex (PIC) (containing SL-1 complex and RNA polymerase I complex) to activate and promote RNA polymerase I-mediated transcription, but disturbs its rDNA promoter binding ability. Collectively, our results demonstrate the role of pNO40 in rRNA biosynthesis regulation by compromising UBF function in rDNA transcription activation with subsequent rRNA synthesis inhibition.

Authors+Show Affiliations

Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan.Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address: ouyang@mail.cgu.edu.tw.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31217076

Citation

Lin, Yen-Ming, et al. "Ectopically Expressed pNO40 Suppresses Ribosomal RNA Synthesis By Inhibiting UBF-dependent Transcription Activation." Biochemical and Biophysical Research Communications, vol. 516, no. 2, 2019, pp. 381-387.
Lin YM, Chu PH, Ouyang P. Ectopically expressed pNO40 suppresses ribosomal RNA synthesis by inhibiting UBF-dependent transcription activation. Biochem Biophys Res Commun. 2019;516(2):381-387.
Lin, Y. M., Chu, P. H., & Ouyang, P. (2019). Ectopically expressed pNO40 suppresses ribosomal RNA synthesis by inhibiting UBF-dependent transcription activation. Biochemical and Biophysical Research Communications, 516(2), pp. 381-387. doi:10.1016/j.bbrc.2019.06.057.
Lin YM, Chu PH, Ouyang P. Ectopically Expressed pNO40 Suppresses Ribosomal RNA Synthesis By Inhibiting UBF-dependent Transcription Activation. Biochem Biophys Res Commun. 2019 Aug 20;516(2):381-387. PubMed PMID: 31217076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ectopically expressed pNO40 suppresses ribosomal RNA synthesis by inhibiting UBF-dependent transcription activation. AU - Lin,Yen-Ming, AU - Chu,Pao-Hsien, AU - Ouyang,Pin, Y1 - 2019/06/16/ PY - 2019/06/04/received PY - 2019/06/11/accepted PY - 2019/6/21/pubmed PY - 2019/6/21/medline PY - 2019/6/21/entrez KW - Nucleolar segregation KW - Ribosomal RNA KW - UBF KW - pNO40 SP - 381 EP - 387 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 516 IS - 2 N2 - Ribosomal RNA (rRNA) production occurs in the nucleolus and is a critical process for ribosome biogenesis which affects protein synthesis capacity and determines the cell growth. Dysregulation of nucleolar homeostasis elicits a nucleolar stress response and is related to disease etiology, indicating that the regulation of nucleolar activity is crucial and tightly coordinated. We previously reported that nucleolar protein pNO40 overexpression mediates SR family splicing factors into the nucleolus and impairs mRNA metabolism, while the function of pNO40 in nucleolar homeostasis is unclear. Here, we demonstrate that overexpression of pNO40 downregulates RNA polymerase I transcription activity, resulting in pre-rRNA synthesis reduction and induces nucleolar segregation, a hallmark of rRNA synthesis inhibition and nucleolar stress response. Moreover, co-immunoprecipitation experiments revealed that ectopically expressed pNO40 interacts with UBF, a master transcription factor involved in pre-initiation complex (PIC) (containing SL-1 complex and RNA polymerase I complex) to activate and promote RNA polymerase I-mediated transcription, but disturbs its rDNA promoter binding ability. Collectively, our results demonstrate the role of pNO40 in rRNA biosynthesis regulation by compromising UBF function in rDNA transcription activation with subsequent rRNA synthesis inhibition. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/31217076/Ectopically_expressed_pNO40_suppresses_ribosomal_RNA_synthesis_by_inhibiting_UBF_dependent_transcription_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(19)31188-X DB - PRIME DP - Unbound Medicine ER -