title: Roles of the nucleolus in the CAG RNA-mediated toxicity.
abstract: The nucleolus is a subnuclear compartment within the cell nucleus that serves as the site for ribosomal RNA (rRNA) transcription and the assembly of ribosome subunits. Apart from its classical role in ribosomal biogenesis, a number of cellular regulatory roles have recently been assigned to the nucleolus, including governing the induction of apoptosis. "Nucleolar stress" is a term that is used to describe a signaling pathway through which the nucleolus communicates with other subcellular compartments, including the mitochondria, to induce apoptosis. It is an effective mechanism for eliminating cells that are incapable of performing protein synthesis efficiently due to ribosome biogenesis defects. The down-regulation of rRNA transcription is a common cause of nucleolar function disruption that subsequently triggers nucleolar stress, and has been associated with the pathogenesis of neurological disorders such as spinocerebellar ataxias (SCAs) and Huntington's diseases (HD). This article discusses recent advances in mechanistic studies of how expanded CAG trinucleotide repeat RNA transcripts trigger nucleolar stress in SCAs, HD and other trinucleotide repeat disorders. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
authors.affiliation: Laboratory of Drosophila Research, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China; Biochemistry Program, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Ho
authors.initials: H
authors.lastname: Tsoi
authors.affiliation: Laboratory of Drosophila Research, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China; Biochemistry Program, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China; Cell and Molecular Biology Program, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China; Molecular Biotechnology Program, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Electronic address: hyechan@cuhk.edu.hk.
authors.forename: Ho Yin Edwin
authors.initials: HY
authors.lastname: Chan
mesh_terms: D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology; D014176:Protein Biosynthesis / Q000235:genetics; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D012335:RNA, Ribosomal; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Nucleolar stress; Nucleolin; Patient fibroblast; Polyglutamine disease; UCE methylation; p53