LncRNA CCTT-mediated RNA-DNA and RNA-protein interactions facilitate the recruitment of CENP-C to centromeric DNA during kinetochore assembly

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 elu...

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Published in:Molecular cell 2022-11, Vol.82 (21), p.4018-4032.e9
Main Authors: Zhang, Chong, Wang, Dongpeng, Hao, Yajing, Wu, Shuheng, Luo, Jianjun, Xue, Yuanchao, Wang, Di, Li, Guohong, Liu, Lihui, Shao, Changwei, Li, Huiyan, Yuan, Jinfeng, Zhu, Maoxiang, Fu, Xiang-Dong, Yang, Xiao, Chen, Runsheng, Teng, Yan
Format: Article
Language:English
Subjects:
aneuploidy
CENP-C recruitment
centromere
lncRNA
mitotic defects
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Summary: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. [Display omitted] •Chromosome 17-derived lncRNA, CCTT, specifically localizes on all centromeres•CCTT interacts with CENP-C to facilitate its recruitment to centromeres•CCTT targets centromeres likely via the formation of RNA-DNA triplex on cenDNA•Depletion of CCTT induces severe mitotic defects and aneuploidy Zhang et al. identify a non-centromere-derived long non-coding RNA, CCTT, that plays a vital role in kinetochore assembly at centromeres in trans. The authors show that CCTT localizes to all centromeres via the formation of RNA-DNA triplex and specifically interacts with CENP-C for its recruitment to centromeres.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2022.09.022