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Unwinding the roles of DEAD-box RNA helicases DDX39A and DDX39B in alternative RNA splicing

ABSTRACT: Dead-box RNA helicases are crucial in mRNA processing, specifically in RNA splicing. Our previous work has shown that DDX39B is responsible for regulating the splicing of IL7R exon 6 and several FOXP3 introns, which rely on DDX39B's helicase and ATPase activities, respectively [this is not accurate since exon 6 also must require the ATPase activity, which is required for helicase activity]. In this study, we aimed to investigate whether DDX39A, a highly homologous paralog of DDX39B, plays a similar role in regulating alternative RNA splicing. We find that DDX39A and DDX39B have significant redundancy in their gene targets, however, DDX39A is incapable of complementing defective splicing of IL7R exon 6 when DDX39B is knockdown. Conversely, overexpressing DDX39A can rescue FOXP3 intron 11 splicing under DDX39B-depleted conditions. In this work we also confirm that introns containing C-rich/U-poor polypyrimidine tract are very sensitive to DDX39B levels. We also observed that cassette exons with C-rich/U-poor py tracts in upstream introns were also sensitive to DDX39B levels and were skipped more upon depletion of DDX39B, but not DDX39A. Among the introns retained more upon DDX39A and DDX39B depletion were DDX39A and DDX39B intron 6, which depend on DDX39A and DDX39B levels, respectively. Therefore, we identified an autoregulatory mechanism through which DDX39A and DDX39B control their respective expression. This study presents evidence that while DDX39A and DDX39B differentially impact certain RNA splicing events, they have many shared targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253261 | GEO | 2024/05/29

REPOSITORIES: GEO

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The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate

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The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate

Project description:The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate

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Suppression of DDX39B sensitizes ovarian cancer cells to DNA-damaging chemotherapeutic agents via destabilizing BRCA1 mRNA

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Homo sapiens

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2014-08-14 | E-GEOD-59327 | biostudies-arrayexpress

The exon junction complex controls transposable element activity by ensuring the faithful splicing of the piwi transcript

Project description:The exon junction complex (EJC) is a highly conserved ribonucleoprotein complex which binds RNAs at a late stage of the splicing reaction and remains associated following export to the cytoplasm. This complex is involved in several cellular post-transcriptional processes including mRNA localization, translation and degradation. The EJC plays an additional role in the splicing of a subset of genes in Drosophila and in human cells but the underlying mechanism remains to be elucidated. Here, we have found a novel function for the EJC and its splicing subunit RnpS1 in preventing transposon accumulation in both Drosophila germline and surrounding follicular cells. This function is mediated specifically through the control of the splicing of the piwi transcript. In absence of RnpS1 one of the piwi intron is retained. This intron contains a weak 5’ splice site as well as degenerate transposon fragments, reminiscent of heterochromatic introns. In addition, we identified a small A/T rich region, which alters its polypyrimidine tract (PPT) and confers the RnpS1’s dependency. Finally, we showed that the removal of this intron by RnpS1 requires the initial splicing of the flanking introns, suggesting a model in which the EJC facilitates the splicing of challenging introns following its initial deposition to adjacent exon junctions. In total there are 4 different conditions. Comparisons were made between piwi mutant vs control piwi and rnps1 KD vs controls RnpS1

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