Department of Dermatology, Ulm University, James-Franck Ring N27, 89081 Ulm, Germany.
Cells. 2019 Jun 4;8(6):534. doi: 10.3390/cells8060534.
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.
核仁组织围绕 RNA 聚合酶 I（RNA Pol I）的转录位点进行。该酶的 rDNA 转录是核糖体生物发生的关键步骤，核糖体的大多数组装和成熟过程都是共转录的。因此，rRNA 转录和加工的干扰会导致核糖体功能障碍。核仁功能障碍最近在儿童经典早衰症、Hutchinson-Gilford 综合征（HGPS）中被描述，其特征是严重的早衰迹象，包括动脉粥样硬化、脱发和骨质疏松症。核糖体生物发生的失调和核仁增大不仅是 HGPS 患者的特征，也存在于“正常”衰老个体的成纤维细胞中。Cockayne 综合征（CS）也以早衰的迹象为特征，包括皮下脂肪丧失、脱发和白内障。已经表明，所有导致 CS 的基因突变的基因都参与 RNA Pol I 的 rDNA 转录。核糖体生物发生的紊乱会影响线粒体，并转化为翻译保真度降低的核糖体，导致内质网（ER）应激和细胞凋亡。因此，人们推测，导致核糖体生物发生过程的疾病相关干扰可能比预期的更为常见。
