The human PAF complex coordinates transcription with events downstream of RNA synthesis

Genes Dev. 2005 Jul 15;19(14):1668-73. doi: 10.1101/gad.1292105.

Abstract

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates 3'-5' mRNA degradation. However, hSKI complex localizes to both nucleus and cytoplasm. Immunoprecipitation experiments revealed that hPAF and hSKI complexes interact, and ChIP experiments demonstrated that hSKI associates with transcriptionally active genes dependent on the presence of hPAF. Thus, in addition to coordinating events during transcription (initiation, promoter clearance, and elongation), hPAF also coordinates events in RNA quality control.

Publication types

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

MeSH terms

  • HeLa Cells
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • In Vitro Techniques
  • Methylation
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Subunits
  • RNA / biosynthesis*
  • RNA / genetics
  • RNA Polymerase II / metabolism
  • Transcription, Genetic*
  • Transcriptional Elongation Factors / chemistry
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism

Substances

  • Histones
  • Multiprotein Complexes
  • Nuclear Proteins
  • Protein Subunits
  • Transcriptional Elongation Factors
  • RNA
  • RNA Polymerase II