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Metastasis-repressive CircRNA MASCOT Regulates Distribution of the Splicing Factor hnRNP M

ABSTRACT: Alternative splicing (AS) diversifies the transcriptome complexity and is usually hijacked by cancer cells. Here, we identified heterogeneous nuclear ribonucleoprotein M (hnRNP M) as an indispensable contributor to EMT-related AS reprogramming, whose sub-nuclear distribution of hnRNP M is altered in metastatic tumors. Upon TGFβ stimulation, hnRNP M trends to disassociate with a circRNA called MASCOT (hnRNP M-ASsociated Circular RNA Of TGFβ) that demonstrated an impressive inhibitory effect on EMT process and tumor metastasis. Mechanistically, the anti-metastatic effect of MASCOT is attributed to not only its competition with U2 RNA splicing factors to recruit hnRNP M in the nucleoplasm, but also the anchorage of hnRNP M with nucleolin into the nucleolus to cause a temporospatial separation of hnRNP M from spliceosome. Moreover, the correlation between MASCOT expression and hnRNP M sub-nuclear localization was validated in clinical specimens. Our study deciphers the regulatory codes controlling AS networks and highlights MASCOT as a promising therapeutic to treat metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165576 | GEO | 2022/09/10

REPOSITORIES: GEO

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Metastasis-repressive CircRNA MASCOT Regulates Distribution of the Splicing Factor hnRNP M

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