Maf1, a new player in the regulation of human RNA polymerase III transcription

PLoS One. 2006 Dec 27;1(1):e134. doi: 10.1371/journal.pone.0000134.

Abstract

Background: Human RNA polymerase III (pol III) transcription is regulated by several factors, including the tumor suppressors P53 and Rb, and the proto-oncogene c-Myc. In yeast, which lacks these proteins, a central regulator of pol III transcription, called Maf1, has been described. Maf1 is required for repression of pol III transcription in response to several signal transduction pathways and is broadly conserved in eukaryotes.

Methodology/principal findings: We show that human endogenous Maf1 can be co-immunoprecipitated with pol III and associates in vitro with two pol III subunits, the largest subunit RPC1 and the alpha-like subunit RPAC2. Maf1 represses pol III transcription in vitro and in vivo and is required for maximal pol III repression after exposure to MMS or rapamycin, treatments that both lead to Maf1 dephosphorylation.

Conclusions/significance: These data suggest that Maf1 is a major regulator of pol III transcription in human cells.

Publication types

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

MeSH terms

  • Base Sequence
  • Cell Line
  • DNA Primers / genetics
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Methyl Methanesulfonate / pharmacology
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Subunits
  • Proto-Oncogene Mas
  • RNA Interference
  • RNA Polymerase I / genetics
  • RNA Polymerase II / genetics
  • RNA Polymerase III / chemistry
  • RNA Polymerase III / genetics*
  • RNA Polymerase III / metabolism
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • TATA-Binding Protein Associated Factors / metabolism
  • Transcription, Genetic / drug effects

Substances

  • BRF1 protein, human
  • DNA Primers
  • MAF1 protein, human
  • MAS1 protein, human
  • Protein Subunits
  • Proto-Oncogene Mas
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • TATA-Binding Protein Associated Factors
  • RNA, Transfer
  • Methyl Methanesulfonate
  • RNA Polymerase II
  • RNA Polymerase I
  • RNA Polymerase III