Maf1, a New Player in the Regulation of Human RNA Polymerase III Transcription

Jaime H Reina,Teldja N Azzouz,Nouria Hernandez

doi:10.1371/journal.pone.0000134

Jaime H Reina, Teldja N Azzouz + Show 1 more

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https://doi.org/10.1371/journal.pone.0000134

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Journal: PloS one	Publication Date: Dec 27, 2006
Citations: 136	License type: CC BY 4.0

Affiliation: University of Lausanne

Abstract

BackgroundHuman 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 FindingsWe 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 α-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/SignificanceThese data suggest that Maf1 is a major regulator of pol III transcription in human cells.

Highlights

RNA polymerase III is responsible for the transcription of various short genes encoding untranslated RNAs involved in the maturation of other RNA molecules and in protein biosynthesis
To examine whether human Maf1 is a negative regulator of polymerase III (pol III) transcription, we first tested its effects on pol III transcription in a HeLa cell extract
Upon addition of increasing amounts of recombinant Maf1 produced in E. coli, transcription from all types of pol III promoters, but not from the pol II Adenovirus 2 (Ad2) major late (ML) promoter, was severely depressed

Summary

Introduction

RNA polymerase III (pol III) is responsible for the transcription of various short genes encoding untranslated RNAs involved in the maturation of other RNA molecules and in protein biosynthesis These untranslated RNAs are essential for cell growth and proliferation, and are often abundant and stable. The core type 3 promoters are composed of a proximal element (PSE) and a TATA box that recruit, respectively, the multisubunit complex SNAPc and the TBP component of Brf2TFIIIB, an activity similar to Brf1-TFIIIB except that Brf is replaced by another TFIIB-related factor referred to as Brf (see [1,4,5] for reviews). 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 Maf, has been described. These data suggest that Maf is a major regulator of pol III transcription in human cells

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