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Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias?

Department of Dermatology, Ulm University, James-Franck Ring N27, 89081 Ulm, Germany
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Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Cells 2019, 8(6), 534; https://doi.org/10.3390/cells8060534
Received: 22 April 2019 / Revised: 21 May 2019 / Accepted: 2 June 2019 / Published: 4 June 2019
(This article belongs to the Special Issue Nucleolar Organization and Functions in Health and Disease)
The nucleolus organizes around the sites of transcription by RNA polymerase I (RNA Pol I). rDNA transcription by this enzyme is the key step of ribosome biogenesis and most of the assembly and maturation processes of the ribosome occur co-transcriptionally. Therefore, disturbances in rRNA transcription and processing translate to ribosomal malfunction. Nucleolar malfunction has recently been described in the classical progeria of childhood, Hutchinson–Gilford syndrome (HGPS), which is characterized by severe signs of premature aging, including atherosclerosis, alopecia, and osteoporosis. A deregulated ribosomal biogenesis with enlarged nucleoli is not only characteristic for HGPS patients, but it is also found in the fibroblasts of “normal” aging individuals. Cockayne syndrome (CS) is also characterized by signs of premature aging, including the loss of subcutaneous fat, alopecia, and cataracts. It has been shown that all genes in which a mutation causes CS, are involved in rDNA transcription by RNA Pol I. A disturbed ribosomal biogenesis affects mitochondria and translates into ribosomes with a reduced translational fidelity that causes endoplasmic reticulum (ER) stress and apoptosis. Therefore, it is speculated that disease-causing disturbances in the process of ribosomal biogenesis may be more common than hitherto anticipated. View Full-Text
Keywords: nucleolus; aging; Hutchinson–Gilford Progeria syndrome; Cockayne syndrome; trichothiodystrophy; RNA polymerase I; ribosome; translational fidelity nucleolus; aging; Hutchinson–Gilford Progeria syndrome; Cockayne syndrome; trichothiodystrophy; RNA polymerase I; ribosome; translational fidelity
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Phan, T.; Khalid, F.; Iben, S. Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias? Cells 2019, 8, 534.

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