State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China.
CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Mol Cell. 2022 Nov 3;82(21):4018-4032.e9. doi: 10.1016/j.molcel.2022.09.022.
Kinetochore assembly on centromeres is central for chromosome segregation, and defects in this process cause mitotic errors and aneuploidy. Besides the well-established protein network, emerging evidence suggests the involvement of regulatory RNA in kinetochore assembly; however, it has remained elusive about the identity of such RNA, let alone its mechanism of action in this critical process. Here, we report CCTT, a previously uncharacterized long non-coding RNA (lncRNA) transcribed from the arm of human chromosome 17, which plays a vital role in kinetochore assembly. We show that CCTT highly localizes to all centromeres via the formation of RNA-DNA triplex and specifically interacts with CENP-C to help engage this blueprint protein in centromeres, and consequently, CCTT loss triggers extensive mitotic errors and aneuploidy. These findings uncover a non-centromere-derived lncRNA that recruits CENP-C to centromeres and shed critical lights on the function of centromeric DNA sequences as anchor points for kinetochore assembly.
着丝粒上的动粒组装对于染色体分离至关重要，该过程中的缺陷会导致有丝分裂错误和非整倍体。除了已确立的蛋白质网络外，新出现的证据表明调节 RNA 参与了动粒组装；然而，关于这种 RNA 的身份，更不用说其在这个关键过程中的作用机制，仍然难以捉摸。在这里，我们报告了 CCTT，这是一种以前未被表征的来自人类染色体 17 臂的长非编码 RNA（lncRNA），它在动粒组装中起着至关重要的作用。我们表明，CCTT 通过形成 RNA-DNA 三链体高度定位于所有着丝粒，并特异性地与 CENP-C 相互作用，帮助将这种蓝图蛋白结合到着丝粒上，因此，CCTT 的缺失会引发广泛的有丝分裂错误和非整倍体。这些发现揭示了一种非着丝粒衍生的 lncRNA，它将 CENP-C 招募到着丝粒上，并为着丝粒组装作为动粒组装的锚定点的着丝粒 DNA 序列的功能提供了重要线索。
