Mammalian Maf1 Is a Negative Regulator of Transcription by All Three Nuclear RNA Polymerases

Abstract

Most eukaryotic transcriptional regulators act in an RNA polymerase (Pol)-selective manner.Here we show that the human Maf1 protein negatively regulates transcription by all three nuclear Pols. Changes in Maf1 expression affect Pol I-and Pol III-dependent transcription in human glioblastoma lines. These effects are mediated, in part, through the ability of Maf1 to repress transcription of the TATA binding protein, TBP. Maf1 targets an Elk-1-binding site in the TBP promoter, and its occupancy of this region is reciprocal with that of Elk-1. Similarly, Maf1 occupancy of Pol III genes is inversely correlated with that of the initiation factor TFIIIB and Pol III. The phenotypic consequences of reducing Maf1 expression include changes in cell morphology and the accumulation of actin stress fibers, whereas Maf1 overexpression suppresses anchorage-independent growth. Together with the ability of Maf1 to reduce biosynthetic capacity, these findings support the idea that Maf1 regulates the transformation state of cells.

Covalent Small Ubiquitin-like Modifier (SUMO) Modification of Maf1 Protein Controls RNA Polymerase III-dependent Transcription Repression

“…Expression plasmids for Myc-SUMO1 and Myc-SUMO2 , which are relatively resistant to deSUMOylases, were kindly provided by Dr. David Ann. The pcDNA3-Maf1HA expression vector was previously described (6). Ubc9 and SENP1 siRNAs were previously described (14,15).…”

“…In addition, Maf1 prevents transcription reinitiation by binding to RNA pol III during elongation (5). In contrast to yeast Maf1, mammalian Maf1 has broader functions including direct regulation of both RNA pol III-dependent and pol II-dependent transcription (6). Maf1 represses the expression of TBP, the central transcription initiation factor.…”

“…Increased cellular concentrations of TBP have been shown to induce cell proliferation (7) and oncogenic transformation (8). The fact that Maf1 represses genes involved in oncogenesis and that it suppresses anchorage-independent growth (6) suggests that Maf1 may function as a tumor suppressor. This underscores the importance of understanding the molecular mechanisms that control Maf1 function.…”

Maf1, repressor of tRNA transcription, is involved in the control of gluconeogenetic genes in Saccharomyces cerevisiae

“…Because of the critical importance of Maf1 in Pol III transcription regulation in yeast and human (Boguta 2013;Acker et al, 2013;Johnson et al, 2007), secondary effects of Maf1 inactivation are anticipated. One reliable suggestion of cellular processes apart from Pol III transcription that are affected by Maf1 comes from genetic analysis of maf1 mutants.…”

“…Possibly Maf1 by itself could be involved in the FBP1 expression. Maf1 has been previously shown to modulate some Pol II genes in humans (Johnson et al, 2007). Genome-wide analysis of Maf1 occupancy in yeast identified the …”