RNA splicing aberrations associated with point mutation at the exon 6/intron 6 junction. Diagrammatic depiction of aberrant splicing in tumor no. 4 due to RNA editing. Both the wild-type (WT) and abnormally spliced transcripts (MUT) are shown (Figure 3Aii). The point mutation in the consensus splice donor sequence (underlined) at the exon 6/intron 6 junction (u → a at position +2) is indicated, along with the sequence chromatogram of cDNA showing the editing U(T)-to-A conversion absent in genomic DNA. The cryptic splice donor site in intron 6 used in the tumor is shown in italics. The 49-bp intron 6 sequence inserted in the tumor transcripts and the resulting premature translation termination are indicated. The predicted structures of PRDM1α and PRDM1β are shown along with their functional domains. Both wild-type and truncated PRDM1 proteins are expected to be produced. (B) Partial cDNA nucleotide sequence of transcripts showing retention of intron 6 sequence in tumor no. 4. The U(T) → A point mutation inactivating the normal consensus splice donor site (underlined) at the exon 6/intron 6 junction is indicated. The intron 6 cryptic splice donor site and the splice acceptor site at the intron 6/exon7 junction used in the tumors are in italics. The retained 49-nt intron 6 sequence is shown (solid arrow), and the distance between its 3′ end and the 5′ end of exon 7 is indicated (362 bp). The premature translation termination codon and the novel peptide sequence predicted from the intron 6 sequence are in bold and italics, respectively. The first 2 zinc fingers (ZF1 and ZF2) that remain in the truncated protein are boxed, with their boundaries marked by arrowheads. A minority of the transcripts used an upstream cryptic splice donor site (dotted underline) and retains only the first 18 nucleotides of intron 6 (see text). The encoded protein is not truncated and has an additional 6 amino acids (ERSIFW).