Transcriptome Sequencing Reveals Potential Mechanism of Cryptic 3’ Splice Site Selection in SF3B1-mutated Cancers

by Christopher DeBoever, Emanuela M. Ghia, Peter J. Shepard, Laura Rassenti, Christian L. Barrett, Kristen Jepsen, Catriona H. M. Jamieson, Dennis Carson, Thomas J. Kipps, Kelly A. Frazer Mutations in the splicing factor SF3B1 are found in several cancer types and have been associated with various splicing defects. Using transcriptome sequencing data from chronic lymphocytic leukemia, breast cancer and uveal melanoma tumor samples, we show that hundreds of cryptic 3’ splice sites (3’SSs) are used in cancers with SF3B1 mutations. We define the necessary sequence context for the observed cryptic 3’ SSs and propose that cryptic 3’SS selection is a result of SF3B1 mutations causing a shift in the sterically protected region downstream of the branch point. While most cryptic 3’SSs are present at low frequency (
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research