Molecular Cell, 3 November, 2022, DOI：https://doi.org/10.1016/j.molcel.2022.09.022
LncRNA CCTT-mediated RNA-DNA and RNA-protein interactions facilitate the recruitment of CENP-C to centromeric DNA during kinetochore assembly
Chong Zhang, Dongpeng Wang, Yajing Hao, Shuheng Wu, Jianjun Luo, Yuanchao Xue, Di Wang, Guohong Li, Lihui Liu, Changwei Shao, Huiyan Li, Jinfeng Yuan, Maoxiang Zhu, Xiang-Dong Fu, Xiao Yang, Runsheng Chen, Yan Teng
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.