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Competition between Pre-mRNAs for the Splicing Machinery Drives Global Regulation of Splicing

Author:
Munding, Elizabeth M., Shiue, Lily, Katzman, Sol, Donohue, John Paul, Ares, Manuel
Source:
Molecular cell 2013 v.51 pp. 338-348
ISSN:
1097-2765
Subject:
eukaryotic cells, gene expression regulation, genes, meiosis, microRNA, mutation, spliceosomes, transcription factors, vegetative cells, yeasts
Abstract:
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.
Agid:
1047852