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

被引：95

作者：

Ashton-Beaucage, Dariel ^{[1
]}

Udell, Christian M. ^{[1
]}

Lavoie, Hugo ^{[1
]}

Baril, Caroline ^{[1
]}

Lefrancois, Martin ^{[1
]}

Chagnon, Pierre ^{[1
]}

Gendron, Patrick ^{[1
]}

Caron-Lizotte, Olivier ^{[1
]}

Bonneil, Eric ^{[1
]}

Thibault, Pierre ^{[1
,3
]}

Therrien, Marc ^{[1
,2
]}

机构：

[1] Univ Montreal, Inst Res Immunol & Canc, Lab Intracellular Signaling, Montreal, PQ H3C 3J7, Canada

[2] Univ Montreal, Dept Pathol & Biol Cellulaire, Montreal, PQ H3C 3J7, Canada

[3] Univ Montreal, Dept Chim, Montreal, PQ H3C 3J7, Canada

来源：

CELL | 2010年 / 143卷 / 02期

关键词：

PROTEIN-TYROSINE-PHOSPHATASE; OSKAR MESSENGER-RNA; HUMAN RNPS1; MAMMALIAN-CELLS; MAGO NASHI; RAS; KINASE; GENE; COACTIVATOR; MUTATIONS;

D O I：

10.1016/j.cell.2010.09.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 post-splicing 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.

引用

页码：251 / 262

页数：12

共 72 条

[1] EFFECT ON EYE DEVELOPMENT OF DOMINANT MUTATIONS IN DROSOPHILA HOMOLOG OF THE EGF RECEPTOR [J].