Center for Molecular Biology of RNA, Department of Molecular, Cell & Developmental Biology, Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Mol Cell. 2013 Aug 8;51(3):338-48. doi: 10.1016/j.molcel.2013.06.012. Epub 2013 Jul 25.
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.
在酵母减数分裂过程中，整体剪接效率先增加后减少。在这里，我们提供的证据表明，剪接效率的提高是由于剪接机制竞争的减少。这种调节的时间与核糖体蛋白基因（RPGs）在减数分裂过程中的抑制和重新激活相对应。在营养细胞中，雷帕霉素处理对 RPG 的抑制也会增加剪接效率。IFH1 基因（专门用于 RPG 的转录因子基因）的下调在遗传上抑制了两个剪接体突变 prp11-1 和 prp4-1，并在 prp4-1 细胞中全局恢复了剪接效率。我们得出结论，剪接装置是有限的，而且前信使 RNA 之间存在竞争。因此，前 mRNA 的剪接效率不仅取决于其自身的浓度和对有限剪接因子的亲和力，还取决于竞争前 mRNA 的浓度和亲和力。对于限制加工因子的 RNA 之间的竞争似乎是真核生物中各种转录后控制机制（包括 microRNA (miRNA) 抑制、多聚腺苷酸化和剪接）的普遍条件。
