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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE123956 | GEO | 2020/07/17

REPOSITORIES: GEO

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

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