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

Ashton‐Beaucage, Dariel; Udell, Christian M.; Lavoie, Hugo; Baril, Caroline; Lefrançois, Martin; Chagnon, Pierre; Gendron, Patrick; Caron-Lizotte, Olivier; Bonneil, Éric; Thibault, Pierre; Therrien, Marc

doi:10.1016/j.cell.2010.09.014

Cited by 112 publications

(153 citation statements)

References 79 publications

(94 reference statements)

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“…In Drosophila, it has been shown that the EJC components regulate the splicing of long-intron containing pre-mRNAs, and EJC KD reduced their expression more than short introncontaining pre-mRNAs [27]. We performed the same analysis with HeLa cell transcriptome data but found no correlation between intron length and differential expression level in any KD conditions in human cells (Additional file 17).…”

Section: Ejc Regulates Cassette Exons With Longer Flanking Intronsmentioning

confidence: 82%

“…In addition, the EJC has been shown to be required for the splicing of mapk pre-mRNA and other long introncontaining pre-mRNAs in Drosophila [27,28], and two recent studies revealed that EJC components contribute to the splicing of weak intron 4 of the piwi transcript in Drosophila [29,30]. In Xenopus, eIF4A3 is also required for accurate splicing of ryanodine receptor pre-mRNA [31].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome-wide modulation of splicing by the Exon Junction Complex

2014

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Background: The exon junction complex (EJC) is a dynamic multi-protein complex deposited onto nuclear spliced mRNAs upstream of exon-exon junctions. The four core proteins, eIF4A3, Magoh, Y14 and MLN51, are stably bound to mRNAs during their lifecycle, serving as a binding platform for other nuclear and cytoplasmic proteins. Recent evidence has shown that the EJC is involved in the splicing regulation of some specific events in both Drosophila and mammalian cells.

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Section: Ejc Regulates Cassette Exons With Longer Flanking Intronsmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Transcriptome-wide modulation of splicing by the Exon Junction Complex

2014

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“…Once clamped onto mRNA, the tetrameric core acts as a platform to recruit multiple factors conferring different functions to the EJC as mRNA progresses from splicing to translation. Notably, the EJC contributes in regulating the splicing of specific transcripts (8)(9)(10) and participates in mRNA transport (11). The EJC also plays a major role in nonsense-mediated mRNA decay (NMD) that triggers the decay of aberrant mRNAs containing a premature termination codon (12).…”

mentioning

confidence: 99%

EJC core component MLN51 interacts with eIF3 and activates translation

Chazal

Daguenet

Wendling

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The multiprotein exon junction complex (EJC), deposited by the splicing machinery, is an important constituent of messenger ribonucleoprotein particles because it participates to numerous steps of the mRNA lifecycle from splicing to surveillance via nonsense-mediated mRNA decay pathway. By an unknown mechanism, the EJC also stimulates translation efficiency of newly synthesized mRNAs. Here, we show that among the four EJC core components, the RNA-binding protein metastatic lymph node 51 (MLN51) is a translation enhancer. Overexpression of MLN51 preferentially increased the translation of intron-containing reporters via the EJC, whereas silencing MLN51 decreased translation. In addition, modulation of the MLN51 level in cell-free translational extracts confirmed its direct role in protein synthesis. Immunoprecipitations indicated that MLN51 associates with translation-initiating factors and ribosomal subunits, and in vitro binding assays revealed that MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.

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“…Pol II elongation rates and/or its CTD phosphorylation status might regulate exon tethering in a transcript-specific manner, thus facilitating processing of long intronic sequences. Intriguingly, as splicing of long introns in Drosophila is facilitated by components of the pre-exon junction complex (EJC) (Ashton-Beaucage et al 2010;Roignant and Treisman 2010), this complex might be involved in modulating exon tethering by Pol II in a transcriptspecific manner.…”

Section: Discussionmentioning

confidence: 99%

Intron cleavage affects processing of alternatively spliced transcripts

Pastor

Mas²,

Talotti³

et al. 2011

RNA

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We previously showed that the insertion of a hammerhead ribozyme (Rz) in a critical intronic position between the EDA exon and a downstream regulatory element affects alternative splicing. Here we evaluate the effect of other intronic cotranscriptional cleavage events on alternative pre-mRNA processing using different ribozymes (Rz) and Microprocessor target sequences (MTSs). In the context of the fibronectin EDA minigene, intronic MTSs were cleaved very inefficiently and did not affect alternative splicing or the level of mature transcripts. On the contrary, all hammerhead Rz derivatives and hepatitis d Rz were completely cleaved before a splicing decision and able to affect alternative splicing. Despite the very efficient Rz-mediated cleavage, the levels of mature mRNA were only reduced to~40%. We show that this effect on mature transcripts occurs regardless of the type and intronic position of Rzs, or changes in alternative splicing and exon definition. Thus, we suggest that intron integrity is not strictly required for splicing but is necessary for efficient pre-mRNA biosynthesis.

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

Cited by 112 publications

References 79 publications

Transcriptome-wide modulation of splicing by the Exon Junction Complex

Transcriptome-wide modulation of splicing by the Exon Junction Complex

EJC core component MLN51 interacts with eIF3 and activates translation

Intron cleavage affects processing of alternatively spliced transcripts

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