The Exon Junction Complex Controls the Splicing of mapk and Other Long Intron-Containing Transcripts in Drosophila

SummarySignaling pathways are controlled by a vast array of posttranslational mechanisms. By contrast, little is known regarding the mechanisms that regulate the expression of their core components. We conducted an RNAi screen in Drosophila for factors modulating RAS/MAPK signaling and identified the Exon Junction Complex (EJC) as a key element of this pathway. The EJC binds the exon-exon junctions of mRNAs and thus far, has been linked exclusively to postsplicing events. Here, we report that the EJC is required for proper splicing of mapk transcripts by a mechanism that apparently controls exon definition. Moreover, whole transcriptome and RT-PCR analyses of EJC-depleted cells revealed that the splicing of long intron-containing genes, which includes mapk, is sensitive to EJC activity. These results identify a role for the EJC in the splicing of a subset of transcripts and suggest that RAS/MAPK signaling depends on the regulation of MAPK levels by the EJC.

Graphical AbstractFigure optionsDownload high-quality image (118 K)Download as PowerPoint slideHighlights
► An RNAi screen in Drosophila unveils the EJC as a regulator of RAS/MAPK signaling
► The EJC controls mapk pre-mRNA splicing, which in turn modulates MAPK protein levels
► RNA-seq data links the EJC to the splicing of long intron containing transcripts
► The EJC appears to influence exon definition of long intron containing transcripts