Figure 4

Extensive mRNA isoform loss and intron retention in RRMS. (A) Total exon loss and intron gain events across the genome in RRMS (N = 6) and CTRL (N = 8) were determined from RNA-seq analysis (see Methods). Results are expressed as average normalized counts or reads across known exons and introns in CTRL and RRMS. (B) Percent abundance of transcript alterations in RRMS relative to CTRL PBMC determined from analysis of genome-wide RNA-seq data. (C) Example of intron retention in mRNA encoded by MBP. Green arrows identify exons. Red circles identify retention of intron sequences in mature mRNA in RRMS. Orange and blue arrows identify two isoforms. (D, E) Examples of 5’ mRNA shortening, CSF1R, and 3’ mRNA shortening, NFATC1 in RRMS. Red arrows identify loss of exons in RRMS and green arrows identify exons expressed at equal levels between CTRL and RRMS. (F) Expression levels of individual exons and the MBP intron in CTRL (N = 12) and RRMS (N = 12) was determined by quantitative PCR and normalized to CTRL = 1.0 after normalization to transcript levels of GAPDH, error bars are S.D. * = P <0.05.