Effects of the Paf1 complex and histone modifications on snoRNA 3'-end formation reveal broad and locus-specific regulation

Mol Cell Biol. 2013 Jan;33(1):170-82. doi: 10.1128/MCB.01233-12. Epub 2012 Oct 29.

Abstract

Across diverse eukaryotes, the Paf1 complex (Paf1C) plays critical roles in RNA polymerase II transcription elongation and regulation of histone modifications. Beyond these roles, the human and Saccharomyces cerevisiae Paf1 complexes also interact with RNA 3'-end processing components to affect transcript 3'-end formation. Specifically, the Saccharomyces cerevisiae Paf1C functions with the RNA binding proteins Nrd1 and Nab3 to regulate the termination of at least two small nucleolar RNAs (snoRNAs). To determine how Paf1C-dependent functions regulate snoRNA formation, we used high-density tiling arrays to analyze transcripts in paf1Δ cells and uncover new snoRNA targets of Paf1. Detailed examination of Paf1-regulated snoRNA genes revealed locus-specific requirements for Paf1-dependent posttranslational histone modifications. We also discovered roles for the transcriptional regulators Bur1-Bur2, Rad6, and Set2 in snoRNA 3'-end formation. Surprisingly, at some snoRNAs, this function of Rad6 appears to be primarily independent of its role in histone H2B monoubiquitylation. Cumulatively, our work reveals a broad requirement for the Paf1C in snoRNA 3'-end formation in S. cerevisiae, implicates the participation of transcriptional proteins and histone modifications in this process, and suggests that the Paf1C contributes to the fine tuning of nuanced levels of regulation that exist at individual loci.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / genetics
  • Cyclins / metabolism
  • Gene Expression Regulation, Fungal*
  • Histones / genetics
  • Histones / metabolism*
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Processing, Post-Translational
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • TATA-Box Binding Protein / genetics
  • TATA-Box Binding Protein / metabolism
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitination

Substances

  • Bur2 protein, S cerevisiae
  • CTR9 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cyclins
  • Histones
  • Nuclear Proteins
  • PAF1 protein, S cerevisiae
  • RNA, Small Nucleolar
  • RTF1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • TATA-Box Binding Protein
  • Transcriptional Elongation Factors
  • Methyltransferases
  • Set2 protein, S cerevisiae
  • RAD6 protein, S cerevisiae
  • Ubiquitin-Conjugating Enzymes
  • Cyclin-Dependent Kinases
  • SGV1 protein, S cerevisiae