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RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE123959 | GEO | 2020/07/17

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC7479136 | biostudies-literature

RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [fCLIP-Seq]

Project description:The processing of RNAs by chromatin-associated proteins (CAPs) is highlighted by the latest findings. However, whether and how CAP-RNA interactions regulate cancer biology remain underdefined. Using modified fCLIP-seq technology, we show that, cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, binds bulk transcripts, preferentially at splicing-responsible motifs, influencing the abundance and alternative splicing (AS) of target transcripts, preferentially those encoding mitosis regulators. MTA1 orchestrates the fluctuant pre-mRNA AS kinetics of mitosis regulators, such as ATRX and MYBL2, during mitosis. MTA1 overexpression causes a defective mitotic arrest, leading to aberrant chromosome segregation, and CIN occurrence in cancer cells and clinical tumors, which eventually contributes to tumorigenesis. Hence, we present MTA1 as a pivotal RNA-binding CAP linked to mitosis control in tumorigenesis.

2020-07-17 | GSE123956 | GEO

RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [ChIP-Seq]

2020-07-17 | GSE123955 | GEO

RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [Synchronized RNA-seq]

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RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [Non-synchronized RNA-seq]

2020-07-17 | GSE123957 | GEO

RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing

Project description:RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing

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RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [fCLIP-Seq]

Project description:RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [fCLIP-Seq]

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RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [ChIP-Seq]

Project description:RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [ChIP-Seq]

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RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [Synchronized RNA-seq]

Project description:RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [Synchronized RNA-seq]

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RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [Non-synchronized RNA-seq]

Project description:RNA-binding chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing [Non-synchronized RNA-seq]

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