Translational mechanisms at work in the cohesinopathies
Translational mechanisms at work in the cohesinopathies
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DOI：
10.4161/nucl.22800
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发表时间：
2012-11-01
期刊：
影响因子：
3.7
通讯作者：
Gerton, Jennifer L.
中科院分区：
文献类型：
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作者：
Gerton, Jennifer L.
在染色体分离过程中，由粘附素复合体介导的染色体凝聚力是必不可少的。粘附素及其调节因子的突变与一组被称为粘附素病的人类疾病有关。这些疾病的特征是头部、面部、四肢和心脏发育缺陷，智力低下和发育不良。这些疾病的发育特征不能很好地用染色体分离缺陷来解释，而是与胚胎发育过程中基因表达的变化相一致。因此，理解粘附素疾病的一个中心问题是，粘附素的突变如何导致基因表达的变化。流行的模型之一是粘附素与启动子和增强子的结合直接调节转录。此外，我认为粘附素可能通过翻译机制影响基因的表达。如果是真的，粘附素疾病在病因学上可能与另一组被称为核糖体疾病的人类疾病有关，核糖体生物发生缺陷引起的疾病。通过考虑这种可能性，我们可以更全面地评估粘附性疾病的原因和治疗。
Chromosome cohesion, mediated by the cohesin complex, is essential for the process of chromosome segregation. Mutations in cohesin and its regulators are associated with a group of human diseases known as the cohesinopathies. These diseases are characterized by defects in head, face, limb, and heart development, mental retardation, and poor growth. The developmental features of the diseases are not well explained by defects in chromosome segregation, but instead are consistent with changes in gene expression during embryogenesis. Thus a central question to understanding the cohesinopathies is how mutations in cohesin lead to changes in gene expression. One of the prevailing models is that cohesin binding to promoters and enhancers directly regulates transcription. I propose that in addition cohesin may influence gene expression via translational mechanisms. If true, cohesinopathies may be related in etiology to another group of human diseases known as ribosomopathies, diseases caused by defects in ribosome biogenesis. By considering this possibility we can more fully evaluate causes and treatments for the cohesinopathies.