Transcriptome Sequencing Reveals Potential Mechanism of Cryptic 3’ Splice Site Selection in SF3B1-mutated Cancers
Fig 3
Location of predicted branch point relative to cryptic and canonical 3’SSs and model of cryptic 3’SS selection.
(A) Distance from highest scoring BP predicted for associated canonical 3’SSs to the corresponding proximal cryptic 3’SSs. A negative distance indicates that the cryptic 3’SS is upstream of the BP predicted for the canonical 3’SS. The small spike at 2 bp indicates that in a few cases the adenine in the cryptic 3’SS is predicted to be the BP adenine for the canonical 3’SS. (B) Distance from highest scoring BP predicted for control 3’SSs to downstream intronic AG dinucleotides that are not annotated as 3’SSs. (C) Distance from either highest or second highest scoring BP predicted for canonical 3’SSs to their associated cryptic 3’SSs (see Methods). (D) Model for proximal cryptic 3’SS selection in SF3B1 mutants. yTnAy is the human BP motif. AG dinucleotides located at the edge of the sterically protected region can be used as 3’SSs in SF3B1 mutants (star). AG dinucleotides located in the protected or competitive regions (X’s) are respectively sterically hindered from being selected as 3’SSs or out-competed by the canonical 3’SS. Distance from predicted BP to 3’SS for (E) associated canonical 3’SSs and (F) control 3’SSs (see Methods) is significantly different (p < 10-23, Mann Whitney U).