title: Computational discovery of transcriptional regulatory modules in fungal ribosome biogenesis genes reveals novel sequence and function patterns.
abstract: Genes involved in ribosome biogenesis and assembly (RBA) are responsible for ribosome formation. In Saccharomyces cerevisiae, their transcription is regulated by two dissimilar DNA motifs. We were interested in analyzing conservation and divergence of RBA transcription regulation machinery throughout fungal evolution. We have identified orthologs of S. cerevisiae RBA genes in 39 species across fungal phylogeny and searched upstream regions of these gene sets for DNA sequences significantly similar to S. cerevisiae RBA regulatory motifs. In addition to confirming known motif arrangements comprising two different motifs in a set of S. cerevisiae close relatives or two instances of the same motif (that we refer to as modules), we have also discovered novel modules in a group of fungi closely related to Neurospora crassa. Despite a single nucleotide difference between consensus sequences of RBA motifs, modules associated with S, cerevisiae group and N. crassa group displayed consistently different characteristics with respect to preferred module organization and several other module properties. For a given species, we have found a correlation between the configuration of the RBA module and significant enrichment in a set of specific Gene Ontology biological processes. We have identified several likely new candidates for a role in ribosome biogenesis in S. cerevisiae based on the combined evidence of RBA module presence in the upstream regions, functional annotation information and microarray expression profiles. We believe that this approach will be useful in terms of generating hypotheses about functional roles of genes for which only fragmentary data from a single source are available.
authors.affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Viktor
authors.initials: V
authors.lastname: Martyanov
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gross
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D019295:Computational Biology; D015966:Gene Expression Regulation, Fungal; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D009492:Neurospora crassa / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D001678:Organelle Biogenesis; D010802:Phylogeny; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors
references.citation: BMC Genomics. 2008 Sep 24;9:442
references.pmid: 18816399
references.citation: Nucleic Acids Res. 1998 Jan 1;26(1):73-9
references.pmid: 9399804
references.citation: Genome Res. 2009 Apr;19(4):556-66
references.pmid: 19158363
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D491-6
references.pmid: 17962297
references.citation: J Biol Chem. 2007 Sep 7;282(36):26623-8
references.pmid: 17616518
references.citation: Nat Genet. 1999 Jul;22(3):281-5
references.pmid: 10391217
references.citation: Mol Syst Biol. 2006;2:2006.0012
references.pmid: 16738557
references.citation: J Mol Biol. 2000 Mar 10;296(5):1205-14
references.pmid: 10698627
references.citation: J Biol Chem. 1991 Aug 15;266(23):15300-7
references.pmid: 1869554
references.citation: Cell. 2004 Apr 16;117(2):185-98
references.pmid: 15084257
references.citation: BMC Bioinformatics. 2007 Jul 12;8:249
references.pmid: 17626633
references.citation: BMC Evol Biol. 2006 Nov 22;6:99
references.pmid: 17121679
references.citation: Nucleic Acids Res. 2004 Oct 14;32(18):5539-45
references.pmid: 15486203
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3593-6
references.pmid: 12824373
references.citation: Microbiology (Reading). 2008 Jan;154(Pt 1):337-346
references.pmid: 18174152
references.citation: Bioinformatics. 2007 Oct 15;23(20):2692-9
references.pmid: 17724061
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19928-33
references.pmid: 19901341
references.citation: Genome Res. 2002 Nov;12(11):1723-31
references.pmid: 12421759
references.citation: Mol Cell Biol. 2001 Dec;21(24):8638-50
references.pmid: 11713296
references.citation: PLoS Genet. 2009 Apr;5(4):e1000449
references.pmid: 19360118
references.citation: Nat Genet. 2001 Oct;29(2):153-9
references.pmid: 11547334
references.citation: Curr Opin Microbiol. 2009 Dec;12(6):655-63
references.pmid: 19875326
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W253-8
references.pmid: 17478497
references.citation: Yeast. 2006 Mar;23(4):293-306
references.pmid: 16544271
references.citation: Science. 2002 Jul 19;297(5580):395-400
references.pmid: 12089449
references.citation: Proc Natl Acad Sci U S A. 2005 May 17;102(20):7203-8
references.pmid: 15883364