Paf1 Has Distinct Roles in Transcription Elongation and Differential Transcript Fate

Mol Cell. 2017 Feb 16;65(4):685-698.e8. doi: 10.1016/j.molcel.2017.01.006. Epub 2017 Feb 9.

Abstract

RNA polymerase II (Pol2) movement through chromatin and the co-transcriptional processing and fate of nascent transcripts is coordinated by transcription elongation factors (TEFs) such as polymerase-associated factor 1 (Paf1), but it is not known whether TEFs have gene-specific functions. Using strand-specific nucleotide resolution techniques, we show that levels of Paf1 on Pol2 vary between genes, are controlled dynamically by environmental factors via promoters, and reflect levels of processing and export factors on the encoded transcript. High levels of Paf1 on Pol2 promote transcript nuclear export, whereas low levels reflect nuclear retention. Strains lacking Paf1 show marked elongation defects, although low levels of Paf1 on Pol2 are sufficient for transcription elongation. Our findings support distinct Paf1 functions: a core general function in transcription elongation, satisfied by the lowest Paf1 levels, and a regulatory function in determining differential transcript fate by varying the level of Paf1 on Pol2.

Keywords: NET-seq; Paf1; RNA polymerase II; Saccharomyces cerevisiae; TEF-seq; differential mRNP nuclear export; lncRNA; mRNA; nucleosome; transcription elongation.

MeSH terms

  • Active Transport, Cell Nucleus
  • Binding Sites
  • Cell Nucleus / metabolism*
  • Gene Expression Regulation, Fungal
  • Genotype
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Phosphorylation
  • Protein Binding
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • RNA, Fungal / biosynthesis*
  • RNA, Fungal / genetics
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Time Factors
  • Transcription Elongation, Genetic*

Substances

  • Nuclear Proteins
  • PAF1 protein, S cerevisiae
  • RNA, Fungal
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • RNA Polymerase II