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

Mol Cell. 2013 Aug 8;51(3):338-48. doi: 10.1016/j.molcel.2013.06.012. Epub 2013 Jul 25.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Down-Regulation
  • Meiosis / genetics*
  • Protein Serine-Threonine Kinases / genetics
  • RNA Precursors / genetics*
  • RNA Precursors / metabolism*
  • RNA Splicing Factors
  • RNA Splicing*
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Heterogeneous Nuclear / genetics
  • RNA, Heterogeneous Nuclear / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • Ribonucleoprotein, U4-U6 Small Nuclear / genetics
  • Ribosomal Proteins / biosynthesis
  • Ribosomal Proteins / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / biosynthesis
  • Saccharomyces cerevisiae Proteins / genetics
  • Sequence Analysis, RNA
  • Sirolimus / pharmacology
  • Spliceosomes / genetics
  • Trans-Activators / biosynthesis
  • Transcription, Genetic

Substances

  • IFH1 protein, S cerevisiae
  • PRP11 protein, S cerevisiae
  • RNA Precursors
  • RNA Splicing Factors
  • RNA, Fungal
  • RNA, Heterogeneous Nuclear
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • PRP4 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Sirolimus

Associated data

  • GEO/GSE44219