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Competition between Pre-mRNAs for the splicing machinery drives global regulation of splicing

机译:前mRNA在剪接机器之间的竞争推动了对剪接的全球监管

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During meiosis in yeast, global splicing efficiency increases and then decreases. Here we provide evidence that splicing improves due to reduced competition for the splicing machinery. The timing of this regulation corresponds to repression and reactivation of ribosomal protein genes (RPGs) during meiosis. In vegetative cells, RPG repression by rapamycin treatment also increases splicing efficiency. Downregulation of the RPG-dedicated transcription factor gene IFH1 genetically suppresses two spliceosome mutations, prp11-1 and prp4-1, and globally restores splicing efficiency in prp4-1 cells. We conclude that the splicing apparatus is limiting and that pre-messenger RNAs compete. Splicing efficiency of a pre-mRNA therefore depends not just on its own concentration and affinity for limiting splicing factor(s), but also on those of competing pre-mRNAs. Competition between RNAs for limiting processing factors appears to be a general condition in eukaryotes for a variety of posttranscriptional control mechanisms including microRNA (miRNA) repression, polyadenylation, and splicing.
机译:在酵母减数分裂过程中,整体剪接效率先升高然后降低。在这里,我们提供的证据表明,由于减少了对拼接机的竞争,拼接得以改善。该调节的时机对应于减数分裂过程中核糖体蛋白基因(RPG)的抑制和重新激活。在营养细胞中,雷帕霉素处理对RPG的抑制作用还可以提高剪接效率。 RPG专用转录因子基因IFH1的下调在基因上抑制了两个剪接体突变,即prp11-1和prp4-1,并全局恢复了prp4-1细胞的剪接效率。我们得出结论,剪接设备是有限制的,信使前RNA竞争。因此,pre-mRNA的剪接效率不仅取决于其自身的浓度和对限制剪接因子的亲和力,还取决于竞争性pre-mRNA的浓度和亲和力。 RNA之间限制加工因子的竞争似乎是真核生物对多种转录后控制机制(包括microRNA(miRNA)阻遏,聚腺苷酸化和剪接)的一般条件。

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