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The yeast SR-like protein Npl3 links chromatin modification to mRNA processing.

Eukaryotic gene expression involves tight coordination between transcription and pre-mRNA splicing; however, factors responsible for this coordination remain incompletely defined. Here, we explored the genetic, functional, and biochemical interactions of a likely coordinator, Npl3, an SR-like protein in Saccharomyces cerevisiae that we recently showed is required for efficient co-transcriptional recruitment of the splicing machinery. We surveyed the NPL3 genetic interaction space and observed a significant enrichment for genes involved in histone modification and chromatin remodeling. Specifically, we found that Npl3 genetically interacts with both Bre1, which mono-ubiquitinates histone H2B as part of the RAD6 Complex, and Ubp8, the de-ubiquitinase of the SAGA Complex. In support of these genetic data, we show that Bre1 physically interacts with Npl3 in an RNA-independent manner. Furthermore, using a genome-wide splicing microarray, we found that the known splicing defect of a strain lacking Npl3 is exacerbated by deletion of BRE1 or UBP8, a phenomenon phenocopied by a point mutation in H2B that abrogates ubiquitination. Intriguingly, even in the presence of wild-type NPL3, deletion of BRE1 exhibits a mild splicing defect and elicits a growth defect in combination with deletions of early and late splicing factors. Taken together, our data reveal a connection between Npl3 and an extensive array of chromatin factors and describe an unanticipated functional link between histone H2B ubiquitination and pre-mRNA splicing.

Pubmed ID: 23209445

Authors

  • Moehle EA
  • Ryan CJ
  • Krogan NJ
  • Kress TL
  • Guthrie C

Journal

PLoS genetics

Publication Data

December 4, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM081879
  • Agency: NIGMS NIH HHS, Id: GM084279
  • Agency: NIGMS NIH HHS, Id: GM084448
  • Agency: PHS HHS, Id: NIHGM21119
  • Agency: NIGMS NIH HHS, Id: P50 GM081879
  • Agency: NIGMS NIH HHS, Id: R01 GM084279
  • Agency: NIGMS NIH HHS, Id: R01 GM084448

Mesh Terms

  • Chromatin Assembly and Disassembly
  • Endopeptidases
  • Histones
  • Nuclear Proteins
  • RNA Precursors
  • RNA Processing, Post-Transcriptional
  • RNA Splicing
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription, Genetic
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitination