Inhibition of SF3B1 by molecules targeting the spliceosome results in massive aberrant exon skipping.

ABSTRACT: The recent identification of compounds that interact with the spliceosome (sudemycins, spliceostatin A, and meayamycin) indicates that these molecules modulate aberrant splicing via SF3B1 inhibition. Through whole transcriptome sequencing, we have demonstrated that treatment of Rh18 cells with sudemycin leads to exon skipping as the predominant aberrant splicing event. This was also observed following reanalysis of published RNA-seq data sets derived from HeLa cells after spliceostatin A exposure. These results are in contrast to previous reports that indicate that intron retention was the major consequence of SF3B1 inhibition. Analysis of the exon junctions up-regulated by these small molecules indicated that these sequences were absent in annotated human genes, suggesting that aberrant s

SUBMITTER: Wu G 

PROVIDER: S-EPMC6049506 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature