Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing

被引：27

作者：

Liu, Jian ^{[1
,2
]}

Li, Chunxiao ^{[1
,3
]}

Wang, Jinsong ^{[1
]}

Xu, Dongkui ^{[4
]}

Wang, Haijuan ^{[1
]}

Wang, Ting ^{[1
]}

Li, Lina ^{[2
]}

Li, Hui ^{[1
]}

Nan, Peng ^{[1
]}

Zhang, Jingyao ^{[1
]}

Wang, Yang ^{[5
]}

Huang, Changzhi ^{[1
]}

Chen, Dong ^{[6
]}

Zhang, Yi ^{[6
]}

Wen, Tao ^{[2
]}

Zhan, Qimin ^{[1
,7
]}

Ma, Fei ^{[3
]}

Qian, Haili ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Natl Clin Res Ctr Canc, Canc Hosp,Natl Canc Ctr, Beijing 100021, Peoples R China

[2] Capital Med Univ, Beijing Chao Yang Hosp, Med Res Ctr, Beijing 100020, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, Canc Hosp, Natl Canc Ctr,Dept Med Oncol, Beijing 100021, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, Canc Hosp, VIP Dept,Natl Canc Ctr, Beijing 100021, Peoples R China

[5] Dalian Med Univ, Inst Canc Stem Cell, Dalian 116044, Peoples R China

[6] ABLife Inc, Ctr Genome Anal, Wuhan 430075, Peoples R China

[7] Peking Univ Canc Hosp & Inst, Lab Mol Oncol, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

中国国家自然科学基金;

关键词：

HUMAN CELL-CYCLE; TRANSCRIPTION FACTORS; BINDING PROTEINS; GENE; IDENTIFICATION; METASTASIS; RECEPTOR; ELEMENTS; COMPLEX; ATRX;

D O I：

10.1038/s41467-020-18259-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dysregulated alternative splicing (AS) driving carcinogenetic mitosis remains poorly understood. Here, we demonstrate that cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, broadly interacts and co-expresses with RBPs across cancers, contributing to cancerous mitosis-related AS. Using developed fCLIP-seq technology, we show that MTA1 binds abundant transcripts, preferentially at splicing-responsible motifs, influencing the abundance and AS pattern of target transcripts. MTA1 regulates the mRNA level and guides the AS of a series of mitosis regulators. MTA1 deletion abrogated the dynamic AS switches of variants for ATRX and MYBL2 at mitotic stage, which are relevant to mitosis-related tumorigenesis. MTA1 dysfunction causes defective mitotic arrest, leads to aberrant chromosome segregation, and results in chromosomal instability (CIN), eventually contributing to tumorigenesis. Currently, little is known about the RNA splicing during mitosis; here, we uncover that MTA1 binds transcripts and orchestrates dynamic splicing of mitosis regulators in tumorigenesis.

引用

页数：17