title: Drosophila MCRS2 associates with RNA polymerase II complexes to regulate transcription.
abstract: Drosophila MCRS2 (dMCRS2; MCRS2/MSP58 and its splice variant MCRS1/p78 in humans) belongs to a family of forkhead-associated (FHA) domain proteins. Whereas human MCRS2 proteins have been associated with a variety of cellular processes, including RNA polymerase I transcription and cell cycle progression, dMCRS2 has been largely uncharacterized. Recent data show that MCRS2 is purified as part of a complex containing the histone acetyltransferase MOF (males absent on first) in both humans and flies. MOF mediates H4K16 acetylation and regulates the expression of a large number of genes, suggesting that MCRS2 could also have a function in transcription regulation. Here, we show that dMCRS2 copurifies with RNA polymerase II (RNAP II) complexes and localizes to the 5' ends of genes. Moreover, dMCRS2 is required for optimal recruitment of RNAP II to the promoter regions of cyclin genes. In agreement with this, dMCRS2 is required for normal levels of cyclin gene expression. We propose a model whereby dMCRS2 promotes gene transcription by facilitating the recruitment of RNAP II preinitiation complexes (PICs) to the promoter regions of target genes.
authors.affiliation: Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
authors.forename: Ditte Skovaa
authors.initials: DS
authors.lastname: Andersen
authors.forename: Sunil Jayaramaiah
authors.initials: SJ
authors.lastname: Raja
authors.forename: Julien
authors.initials: J
authors.lastname: Colombani
authors.forename: Rachael Louise
authors.initials: RL
authors.lastname: Shaw
authors.forename: Paul Francis
authors.initials: PF
authors.lastname: Langton
authors.forename: Asifa
authors.initials: A
authors.lastname: Akhtar
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tapon
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D016213:Cyclins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C553193:Rcd5 protein, Drosophila; D049452:Green Fluorescent Proteins; D051548:Histone Acetyltransferases; C111063:mof protein, Drosophila; D012319:RNA Polymerase II