Center for Molecular Biology Heidelberg (ZMBH), DKFZ-ZMBH-Alliance, Heidelberg University, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
Center for Molecular Biology Heidelberg (ZMBH), DKFZ-ZMBH-Alliance, Heidelberg University, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
J Mol Biol. 2020 Jul 10;432(15):4257-4269. doi: 10.1016/j.jmb.2020.03.027. Epub 2020 Apr 2.
The most fundamental region of the chromosome for maintaining accurate genome segregation and stability is the centromeric chromatin [1,2]. In this review, we will focus on centromere-derived RNAs (cenRNAs), a crucial component of centromere structure first identified over 40 years ago [3] but only recently investigated in detail. Indeed, centromeric transcription is necessary for the proper formation of CENP-A-containing centromeric chromatin (cen-chromatin) [4-7] and for the formation of pericentromeric heterochromatin [8,9], and the transcripts play a role in the structure and function of the centromere-kinetochore interface [3,7,10]. Furthermore, cenRNA overexpression has been observed in some cancer patients [11-13] and has been shown to drive the formation of breast cancer in a mouse model system [14]. Together, these observations call for a more detailed appraisal of the composition, regulation and function of cenRNAs. In this review, we will first discuss the difficulties underlying the study of cenRNAs, then we identify different domains within the centromeric chromatin before we discuss the role of cenRNAs in the context of these domains.
染色体中维持基因组精确分离和稳定性的最基本区域是着丝粒染色质[1,2]。在这篇综述中，我们将重点介绍着丝粒衍生的 RNA（cenRNA），这是着丝粒结构的一个关键组成部分，早在 40 多年前就被首次发现[3]，但直到最近才被详细研究。事实上，着丝粒转录对于含有 CENP-A 的着丝粒染色质（cen 染色质）[4-7]的正确形成以及着丝粒周围异染色质[8,9]的形成是必要的，并且转录本在着丝粒-动粒界面的结构和功能中发挥作用[3,7,10]。此外，在一些癌症患者中观察到 cenRNA 的过表达[11-13]，并在小鼠模型系统中显示出可驱动乳腺癌的形成[14]。这些观察结果共同呼吁更详细地评估 cenRNA 的组成、调控和功能。在这篇综述中，我们将首先讨论研究 cenRNA 所面临的困难，然后确定着丝粒染色质内的不同区域，然后再讨论 cenRNA 在这些区域的作用。
