title: Structure-function analysis of Hmo1 unveils an ancestral organization of HMG-Box factors involved in ribosomal DNA transcription from yeast to human.
abstract: Ribosome biogenesis is a major metabolic effort for growing cells. In Saccharomyces cerevisiae, Hmo1, an abundant high-mobility group box protein (HMGB) binds to the coding region of the RNA polymerase I transcribed ribosomal RNAs genes and the promoters of ∼70% of ribosomal protein genes. In this study, we have demonstrated the functional conservation of eukaryotic HMGB proteins involved in ribosomal DNA (rDNA) transcription. We have shown that when expressed in budding yeast, human UBF1 and a newly identified Sp-Hmo1 (Schizosaccharomyces pombe) localize to the nucleolus and suppress growth defect of the RNA polymerase I mutant rpa49-Δ. Owing to the multiple functions of both proteins, Hmo1 and UBF1 are not fully interchangeable. By deletion and domains swapping in Hmo1, we identified essential domains that stimulate rDNA transcription but are not fully required for stimulation of ribosomal protein genes expression. Hmo1 is organized in four functional domains: a dimerization module, a canonical HMGB motif followed by a conserved domain and a C-terminal nucleolar localization signal. We propose that Hmo1 has acquired species-specific functions and shares with UBF1 and Sp-Hmo1 an ancestral function to stimulate rDNA transcription.
authors.affiliation: LBME du CNRS, Université de Toulouse, 118 route de Narbonne, F-31000 Toulouse, France, Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse, 118 route de Narbonne, F-31000 Toulouse, France and Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Albert
authors.forename: Christine
authors.initials: C
authors.lastname: Colleran
authors.forename: Isabelle
authors.initials: I
authors.lastname: Léger-Silvestre
authors.forename: Axel B
authors.initials: AB
authors.lastname: Berger
authors.forename: Christophe
authors.initials: C
authors.lastname: Dez
authors.forename: Christophe
authors.initials: C
authors.lastname: Normand
authors.forename: Jorge
authors.initials: J
authors.lastname: Perez-Fernandez
authors.forename: Brian
authors.initials: B
authors.lastname: McStay
authors.forename: Olivier
authors.initials: O
authors.lastname: Gadal
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002466:Cell Nucleolus / Q000378:metabolism; D017124:Conserved Sequence; D004275:DNA, Ribosomal / Q000378:metabolism*; D024002:HMGB Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035463:Pol1 Transcription Initiation Complex Proteins / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012318:RNA Polymerase I / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D004275:DNA, Ribosomal; D024002:HMGB Proteins; C103154:HMO1 protein, S cerevisiae; D006609:High Mobility Group Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C063844:transcription factor UBF; D012318:RNA Polymerase I
references.citation: Yeast. 2006 Feb;23(3):173-83
references.pmid: 16498704
references.citation: Genes Genet Syst. 2003 Jun;78(3):199-209
references.pmid: 12893961
references.citation: EMBO J. 1999 May 4;18(9):2563-79
references.pmid: 10228169
references.citation: Nucleic Acids Res. 2001 Aug 1;29(15):3241-7
references.pmid: 11470882
references.citation: Biochem Soc Symp. 2006;(73):203-16
references.pmid: 16626300
references.citation: EMBO J. 1992 Apr;11(4):1531-42
references.pmid: 1563354
references.citation: Cell. 2008 Oct 17;135(2):308-21
references.pmid: 18957205
references.citation: Genes Dev. 1992 Oct;6(10):1950-63
references.pmid: 1398072
references.citation: EMBO J. 2002 Oct 15;21(20):5498-507
references.pmid: 12374750
references.citation: EMBO J. 1994 Jan 15;13(2):416-24
references.pmid: 8313887
references.citation: J Cell Sci. 1993 Feb;104 ( Pt 2):327-37
references.pmid: 8505363
references.citation: Mol Cell Biol. 2011 Feb;31(3):482-94
references.pmid: 21098118
references.citation: Mol Cell Biol. 1994 May;14(5):2905-13
references.pmid: 8164651
references.citation: Cell. 2009 Sep 4;138(5):870-84
references.pmid: 19737516
references.citation: Mol Cell. 2003 Jul;12(1):135-45
references.pmid: 12887899
references.citation: EMBO J. 1991 Aug;10(8):2297-303
references.pmid: 2065665
references.citation: Nucleic Acids Res. 1999 Feb 15;27(4):1205-13
references.pmid: 9927757
references.citation: EMBO J. 1996 May 1;15(9):2217-26
references.pmid: 8641287
references.citation: J Cell Biol. 2002 Jun 10;157(6):941-51
references.pmid: 12058014
references.citation: J Cell Biol. 2011 Jan 24;192(2):277-93
references.pmid: 21263028
references.citation: Chromosoma. 1999 May;108(2):103-13
references.pmid: 10382072
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12707-12
references.pmid: 16908835
references.citation: EMBO J. 2006 Jul 26;25(14):3310-22
references.pmid: 16858408
references.citation: Epigenetics. 2009 Aug 16;4(6):374-82
references.pmid: 19717978
references.citation: Nucleic Acids Res. 1995 Jun 11;23(11):1912-8
references.pmid: 7596817
references.citation: Mol Cell. 2001 Nov;8(5):1063-73
references.pmid: 11741541
references.citation: Mol Gen Genet. 1984;197(2):345-6
references.pmid: 6394957
references.citation: Gene Expr. 1993;3(3):229-36
references.pmid: 8019125
references.citation: Nat Methods. 2008 Dec;5(12):1031-7
references.pmid: 18978785
references.citation: Cell. 2011 May 13;145(4):543-54
references.pmid: 21565613
references.citation: Mol Cell Biol. 2008 Mar;28(5):1596-605
references.pmid: 18086878
references.citation: J Biol Chem. 2005 Aug 19;280(33):29551-8
references.pmid: 15970593
references.citation: J Biol Chem. 2004 Dec 31;279(53):55234-40
references.pmid: 15507436
references.citation: Genes Dev. 2005 Jan 1;19(1):50-64
references.pmid: 15598984
references.citation: Mol Cell Biol. 2002 Jan;22(2):657-68
references.pmid: 11756560
references.citation: Nucleic Acids Res. 2008 Mar;36(4):1343-57
references.pmid: 18187511
references.citation: Genet Res Int. 2012;2012:276948
references.pmid: 22567380
references.citation: Mol Cell Biol. 2007 Nov;27(22):8015-26
references.pmid: 17875934
references.citation: Mol Cell Biol. 2006 Jul;26(14):5436-48
references.pmid: 16809778
references.citation: Mol Cell. 2010 Aug 27;39(4):583-94
references.pmid: 20797630
references.citation: Genes Dev. 2008 May 1;22(9):1190-204
references.pmid: 18451108
references.citation: EMBO J. 1994 Jan 1;13(1):190-9
references.pmid: 8306961
references.citation: Curr Opin Cell Biol. 2009 Dec;21(6):855-63
references.pmid: 19796927
references.citation: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3180-4
references.pmid: 2014238
references.citation: J Cell Sci. 1999 Nov;112 ( Pt 22):4151-61
references.pmid: 10547374
references.citation: Mol Cell Biol. 2007 Oct;27(19):6686-705
references.pmid: 17646381
references.citation: J Biol Chem. 1996 Dec 27;271(52):33678-85
references.pmid: 8969238
references.citation: Biochemistry. 2010 May 18;49(19):4051-9
references.pmid: 20402481
references.citation: Trends Cell Biol. 2005 Apr;15(4):194-9
references.pmid: 15817375
references.citation: Mol Cell. 2006 Mar 3;21(5):629-39
references.pmid: 16507361
references.citation: Mol Cell Biol. 1997 Apr;17(4):1787-95
references.pmid: 9121426
references.citation: Nucleic Acids Res. 1993 Jul 11;21(14):3329-30
references.pmid: 8341614
references.citation: Mol Cell Biol. 2006 May;26(9):3672-9
references.pmid: 16612005
references.citation: Genes Dev. 1991 Nov;5(11):1957-68
references.pmid: 1936987