Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing
Year: 2020
Type: article
Abstract: 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.
Source: Nature Communications
Authors: Jian Liu, Chunxiao Li, Jinsong Wang, Dongkui Xu, Haijuan Wang, Ting Wang, Lina Li, Hui Li, Peng Nan, Jingyao Zhang, Yang Wang, Changzhi Huang, Dong Chen, Yi Zhang, Tao Wen, Qimin Zhan, Fei Ma, Haili Qian
Institutions: Capital Medical University, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Chao-Yang Hospital, Capital Medical University, State Key Laboratory of Molecular Oncology, Cancer Hospital of Chinese Academy of Medical Sciences, Dalian Medical University, Peking University Cancer Hospital
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Awards: G1682264685, G1738048008, G1816543945, G1828425977, G190126783, G2522945768, G2553768923, G3432494952, G3534839289, G3816411031, G3839353265, G4535478878, MTA1相关细胞因子介导的肿瘤细胞—微环境交互作用在肿瘤转移过程中的效应和机制研究, 肿瘤转移相关蛋白MTA1在核仁中的定位、功能及其与肿瘤的关系研究, G6009196125, G7044377377, G7078819830, G7238363262, 以翻译起始因子eIF3为靶点系统鉴定与验证食管癌中具有潜在编码功能的非编码RNA, G7308143727, G7547835571, G7764307671, G8842435107, G989173828
OpenAlex ID: W3084347127