Identification of FUBP1 As a Long Tail Cancer Driver and Widespread Regulator of Tumor Suppressor and Oncogene Alternative Splicing

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2019 Sep 26

PMID 31553912

Citations 21

Authors

Jessica S Elman

Thomas K Ni

Kristen E Mengwasser

Dexter Jin

Ania Wronski

Stephen J Elledge

Charlotte Kuperwasser

Affiliations

Soon will be listed here.

Abstract

Comprehensive sequencing approaches have allowed for the identification of the most frequent contributors to cancer, known as drivers. They have also revealed a class of mutations in understudied, infrequently altered genes, referred to as "long tail" (LT) drivers. A key challenge has been to find clinically relevant LT drivers and to understand how they cooperate to drive disease. Here, we identified far upstream binding protein 1 (FUBP1) as an LT driver using an in vivo CRISPR screen. FUBP1 cooperates with other tumor suppressor genes to transform mammary epithelial cells by disrupting cellular differentiation and tissue architecture. Mechanistically, FUBP1 participates in regulating N-methyladenosine (mA) RNA methylation, and its loss leads to global changes in RNA splicing and widespread expression of aberrant driver isoforms. These findings suggest that somatic alteration of a single gene involved in RNA splicing and mA methylation can produce the necessary panoply of contributors for neoplastic transformation.

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