The exon junction complex controls the splicing of MAPK and other long intron-containing transcripts in Drosophila.
Signaling 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.
Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada.
Dariel
D
Ashton-Beaucage
Christian M
CM
Udell
Hugo
H
Lavoie
Caroline
C
Baril
Martin
M
Lefrançois
Pierre
P
Chagnon
Patrick
P
Gendron
Olivier
O
Caron-Lizotte
Eric
E
Bonneil
Pierre
P
Thibault
Marc
M
Therrien
D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D007438:Introns; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing; D015398:Signal Transduction
D029721:Drosophila Proteins; D012322:RNA Precursors; D020928:Mitogen-Activated Protein Kinases