Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies

• Published in: Molecular cell Vol. 82; no. 6; pp. 1107 - 1122.e7
• Main Authors: Biancon, Giulia, Joshi, Poorval, Zimmer, Joshua T., Hunck, Torben, Gao, Yimeng, Lessard, Mark D., Courchaine, Edward, Barentine, Andrew E.S., Machyna, Martin, Botti, Valentina, Qin, Ashley, Gbyli, Rana, Patel, Amisha, Song, Yuanbin, Kiefer, Lea, Viero, Gabriella, Neuenkirchen, Nils, Lin, Haifan, Bewersdorf, Joerg, Simon, Matthew D., Neugebauer, Karla M., Tebaldi, Toma, Halene, Stephanie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.03.2022
• Subjects: AML; crosslinking; exons; freCLIP; Humans; introns; Leukemia, Myeloid, Acute - genetics; MDS; mutants; Mutation; Myelodysplastic Syndromes - genetics; nucleotides; precipitin tests; RNA; RNA binding; RNA granules; RNA Splice Sites; RNA Splicing - genetics; RNA-Binding Proteins - genetics; sequence analysis; splicing; Splicing Factor U2AF - genetics; Splicing Factor U2AF - metabolism; stress granules; Stress Granules - metabolism; stress response; U2AF1; AML; stress response; RNA; stress granules; U2AF1; freCLIP; splicing; RNA granules; MDS; RNA binding

Splicing factor mutations are common among cancers, recently emerging as drivers of myeloid malignancies. U2AF1 carries hotspot mutations in its RNA-binding motifs; however, how they affect splicing and promote cancer remain unclear. The U2AF1/U2AF2 heterodimer is critical for 3′ splice site (3′SS)...