MAF1 Human

MAF1 was initially identified in the yeast Saccharomyces cerevisiae through the isolation of a temperature-sensitive mutation, maf1-1, which affected tRNA suppressor efficiency and interacted genetically with pol III . In humans, MAF1 is involved in the repression of pol III transcription, which is responsible for the transcription of various short genes encoding untranslated RNAs. These RNAs are essential for cell growth and proliferation .

Human 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 both in vitro and in vivo and is required for maximal pol III repression after exposure to treatments like methyl methanesulfonate (MMS) or rapamycin, which lead to MAF1 dephosphorylation .

The regulation of pol III transcription by MAF1 is significant because pol III activity is high in rapidly dividing cells and low in resting cells. This regulation ensures that the demand for pol III activity is met according to the cell’s growth and proliferation needs . Additionally, pol III transcription is rapidly inhibited after stresses that arrest cell growth and/or division, such as DNA damage or rapamycin treatment .

Given its role in regulating pol III transcription, MAF1 is a potential target for therapeutic interventions in diseases characterized by uncontrolled cell growth, such as cancer. The ability to modulate MAF1 activity could provide a means to control pol III transcription and, consequently, cell proliferation.