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Updated: Dec 8, 2025

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
Published on: September 15, 2021
Elucidation of the aberrant 3' splice site selection by cancer-associated mutations on the U2AF1
Hisashi Yoshida1, Sam-Yong Park1, Gyosuke Sakashita2
1Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
Abstract:
The accurate exclusion of introns by RNA splicing is critical for the production of mature mRNA. U2AF1 binds specifically to the 3´ splice site, which includes an essential AG dinucleotide. Even a single amino acid mutation of U2AF1 can cause serious disease such as certain cancers or myelodysplastic syndromes. Here, we describe the first crystal structures of wild-type and pathogenic mutant U2AF1 complexed with target RNA, revealing the mechanism of 3´ splice site selection, and how aberrant splicing results from clinically important mutations. Unexpected features of this mechanism may assist the future development of new treatments against diseases caused by splicing errors.
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