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

被引:10
|
作者
Zhang, Chong [1 ]
Wang, Dongpeng [2 ]
Hao, Yajing [2 ,3 ]
Wu, Shuheng [2 ]
Luo, Jianjun [2 ]
Xue, Yuanchao [2 ]
Wang, Di [2 ]
Li, Guohong [4 ]
Liu, Lihui [2 ]
Shao, Changwei [3 ]
Li, Huiyan [5 ]
Yuan, Jinfeng [5 ]
Zhu, Maoxiang [6 ]
Fu, Xiang-Dong [3 ]
Yang, Xiao [1 ]
Chen, Runsheng [2 ]
Teng, Yan [1 ]
机构
[1] Beijing Inst Lifeom, Natl Ctr Prot Sci, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing 102206, Peoples R China
[2] Chinese Acad Sci, Inst Biophys, CAS Key Lab RNA Biol, Beijing 100101, Peoples R China
[3] Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
[4] Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
[5] Natl Ctr Biomed Anal, State Key Lab Prote, Beijing 100039, Peoples R China
[6] Beijing Inst Radiat Med, Beijing Key Lab Radiobiol, Beijing 100850, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
LONG NONCODING RNA; MOLECULAR-MECHANISMS; READ ALIGNMENT; TRIPLE HELICES; A NUCLEOSOMES; TRANSCRIPTION; RECOGNITION; IDENTITY; CELLS; MAP;
D O I
10.1016/j.molcel.2022.09.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 sug-gests 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 pre-viously 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 find-ings 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.
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页码:4018 / +
页数:25
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