Quality control of MATa1 splicing and exon skipping by nuclear RNA degradation

Nucleic Acids Res. 2012 Feb;40(4):1787-96. doi: 10.1093/nar/gkr864. Epub 2011 Oct 22.

Abstract

The MATa1 gene encodes a transcriptional repressor that is an important modulator of sex-specific gene expression in Saccharomyces cerevisiae. MATa1 contains two small introns, both of which need to be accurately excised for proper expression of a functional MATa1 product and to avoid production of aberrant forms of the repressor. Here, we show that unspliced and partially spliced forms of the MATa1 mRNA are degraded by the nuclear exonuclease Rat1p, the nuclear exosome and by the nuclear RNase III endonuclease Rnt1p to prevent undesired expression of non-functional a1 proteins. In addition, we show that mis-spliced forms of MATa1 in which the splicing machinery has skipped exon2 and generated exon1-exon3 products are degraded by the nuclear 5'-3' exonuclease Rat1p and by the nuclear exosome. This function for Rat1p and the nuclear exosome in the degradation of exon-skipped products is also observed for three other genes that contain two introns (DYN2, SUS1, YOS1), identifying a novel nuclear quality control pathway for aberrantly spliced RNAs that have skipped exons.

Publication types

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

MeSH terms

  • Cell Nucleus / enzymology*
  • Exons*
  • Exoribonucleases / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Introns
  • Mutation
  • RNA Splice Sites
  • RNA Splicing*
  • RNA Stability*
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Ribonuclease III / genetics
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Homeodomain Proteins
  • MATA1 protein, S cerevisiae
  • RNA Splice Sites
  • RNA, Messenger
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • RAT1 protein, S cerevisiae
  • Exoribonucleases
  • RNT1 protein, S cerevisiae
  • Ribonuclease III