2019
DOI: 10.3390/cells8060534
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Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias?

Abstract: 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 s… Show more

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Cited by 11 publications
(12 citation statements)
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“…Demirtas et al hypothesized that this excess in ribosome biogenesis occurring in the early phase of development causes energy waste and a general perturbation of cell metabolism, directly contributing to the DS phenotype ( Demirtas 2009 ). Consistently with this view, increased ribosome biogenesis and enlarged nucleoli were described in fibroblasts derived from Hutchinson–Gilford progeria patients and old subjects ( Buchwalter and Hetzer 2017 ; Phan et al, 2019 ) and are considered a hallmark of premature aging. This apparent discrepancy could be explained by the fact that we did not have infants with DS in our cohort.…”
Section: Discussionsupporting
confidence: 58%
“…Demirtas et al hypothesized that this excess in ribosome biogenesis occurring in the early phase of development causes energy waste and a general perturbation of cell metabolism, directly contributing to the DS phenotype ( Demirtas 2009 ). Consistently with this view, increased ribosome biogenesis and enlarged nucleoli were described in fibroblasts derived from Hutchinson–Gilford progeria patients and old subjects ( Buchwalter and Hetzer 2017 ; Phan et al, 2019 ) and are considered a hallmark of premature aging. This apparent discrepancy could be explained by the fact that we did not have infants with DS in our cohort.…”
Section: Discussionsupporting
confidence: 58%
“…As such, transcription of these genes is a major determinant of cell growth, cell cycle progression and cell survival and an essential factor in the formation of hypertrophic diseases such as cancer [1]. Dysregulation of rRNA genes is also the cause of a large range of developmental and neurological disorders that are often also associated with cancer [2][3][4][5][6]. To develop treatment strategies for these diseases it is important that we command an understanding of how these genes are transcribed and regulated.…”
Section: Introductionmentioning
confidence: 99%
“…For example, secondary DNA structures, which are mostly present in rDNA, cannot be properly resolved in CS cells. Ultimately, this could result in premature aging, as it is observed for CS patients [26].…”
Section: Stress Aging and Longevitymentioning
confidence: 95%
“…Phan et al [26] discuss the work on HGPS, Cockayne Syndrome (CS) and related segmental progeroid syndromes that puts the nucleolus in the spotlight of aging research. These model systems exhibit some changes associated with normal aging, but do not display the full range of aging-related physiological decline.…”
Section: Stress Aging and Longevitymentioning
confidence: 99%
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