title: Comparative genomics boosts target prediction for bacterial small RNAs.
abstract: Small RNAs (sRNAs) constitute a large and heterogeneous class of bacterial gene expression regulators. Much like eukaryotic microRNAs, these sRNAs typically target multiple mRNAs through short seed pairing, thereby acting as global posttranscriptional regulators. In some bacteria, evidence for hundreds to possibly more than 1,000 different sRNAs has been obtained by transcriptome sequencing. However, the experimental identification of possible targets and, therefore, their confirmation as functional regulators of gene expression has remained laborious. Here, we present a strategy that integrates phylogenetic information to predict sRNA targets at the genomic scale and reconstructs regulatory networks upon functional enrichment and network analysis (CopraRNA, for Comparative Prediction Algorithm for sRNA Targets). Furthermore, CopraRNA precisely predicts the sRNA domains for target recognition and interaction. When applied to several model sRNAs, CopraRNA revealed additional targets and functions for the sRNAs CyaR, FnrS, RybB, RyhB, SgrS, and Spot42. Moreover, the mRNAs gdhA, lrp, marA, nagZ, ptsI, sdhA, and yobF-cspC were suggested as regulatory hubs targeted by up to seven different sRNAs. The verification of many previously undetected targets by CopraRNA, even for extensively investigated sRNAs, demonstrates its advantages and shows that CopraRNA-based analyses can compete with experimental target prediction approaches. A Web interface allows high-confidence target prediction and efficient classification of bacterial sRNAs.
authors: Genetics and Experimental Bioinformatics, Faculty of Biology, Centre for Biological Systems Analysis, and BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany.
authors: Patrick R
authors: PR
authors: Wright
authors: Andreas S
authors: AS
authors: Richter
authors: Kai
authors: K
authors: Papenfort
authors: Martin
authors: M
authors: Mann
authors: Jörg
authors: J
authors: Vogel
authors: Wolfgang R
authors: WR
authors: Hess
authors: Rolf
authors: R
authors: Backofen
authors: Jens
authors: J
authors: Georg
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D019295:Computational Biology; D004755:Enterobacteriaceae / Q000145:classification / Q000235:genetics; D004926:Escherichia coli / Q000145:classification / Q000235:genetics; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D023281:Genomics / Q000706:statistics & numerical data; D010802:Phylogeny; D012329:RNA, Bacterial / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D019779:Salmonella enterica / Q000145:classification / Q000235:genetics
chemical_list: D012329:RNA, Bacterial
keywords: E. coli; RNA–RNA interaction; regulatory RNA
references: Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20435-40
references: 21059903
references: G3 (Bethesda). 2012 Dec;2(12):1475-95
references: 23275872
references: Mol Microbiol. 2012 Apr;84(1):51-65
references: 22356413
references: Mol Cell. 2012 Sep 28;47(6):943-53
references: 22902561
references: J Biol Chem. 2010 Apr 2;285(14):10690-702
references: 20075074
references: Nucleic Acids Res. 2006 May 22;34(9):2791-802
references: 16717284
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D98-105
references: 21051347
references: J Bacteriol. 2005 Oct;187(20):6962-71
references: 16199566
references: Mol Microbiol. 2006 May;60(4):1058-75
references: 16677314
references: Res Microbiol. 2010 Oct;161(8):694-700
references: 20633642
references: Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12473-8
references: 21742981
references: Mol Microbiol. 2011 Sep;81(5):1144-65
references: 21696468
references: EMBO J. 2010 Sep 15;29(18):3094-107
references: 20683441
references: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12875-80
references: 21768388
references: RNA. 2004 Oct;10(10):1507-17
references: 15383676
references: Nature. 2010 Mar 11;464(7286):250-5
references: 20164839
references: J Bacteriol. 2012 Jan;194(2):346-53
references: 22081393
references: Nat Protoc. 2009;4(1):44-57
references: 19131956
references: Genes Dev. 2012 Apr 1;26(7):726-39
references: 22474262
references: Nat Protoc. 2007;2(10):2366-82
references: 17947979
references: Cold Spring Harb Perspect Biol. 2011 Dec 01;3(12):
references: 20980440
references: Curr Biol. 2001 Jun 26;11(12):941-50
references: 11448770
references: Mol Cell. 2011 Feb 4;41(3):286-97
references: 21292161
references: EMBO J. 2009 Jun 3;28(11):1551-61
references: 19407815
references: EMBO J. 2012 Apr 18;31(8):1961-74
references: 22388518
references: Cell. 2013 Apr 11;153(2):426-37
references: 23582330
references: Nucleic Acids Res. 2013 Jan;41(Database issue):D605-12
references: 23143106
references: Mol Microbiol. 2008 May;68(4):890-906
references: 18399940
references: J Bacteriol. 2011 Jan;193(2):506-15
references: 21097628
references: Mol Microbiol. 2012 May;84(3):414-27
references: 22324810
references: Mol Microbiol. 2012 Apr;84(1):17-35
references: 22289118
references: Mol Microbiol. 2010 Mar;75(5):1215-31
references: 20070527
references: Wiley Interdiscip Rev RNA. 2012 Jan-Feb;3(1):26-36
references: 21793218
references: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W149-54
references: 21672960
references: Antimicrob Agents Chemother. 2010 Sep;54(9):3557-63
references: 20566764
references: Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):E757-64
references: 22383560
references: Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15522-7
references: 21876160
references: Mol Microbiol. 2012 May;84(3):428-45
references: 22458297
references: J Bacteriol. 2009 Jan;191(2):461-76
references: 18978044
references: Mol Cell. 2008 Dec 26;32(6):827-37
references: 19111662
references: Mol Microbiol. 2012 Apr;84(1):36-50
references: 22250746
references: Nucleic Acids Res. 2007 Jan;35(Database issue):D343-6
references: 17135196
references: RNA Biol. 2012 Jul;9(7):954-65
references: 22767260
references: Mol Cell. 2011 Sep 16;43(6):880-91
references: 21925377
references: Nat Struct Mol Biol. 2009 Aug;16(8):840-6
references: 19620966
references: Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2124-9
references: 21245330
references: EMBO J. 2010 Jun 2;29(11):1840-50
references: 20407422
references: Cell Host Microbe. 2010 Jul 22;8(1):116-27
references: 20638647
references: Bioinformatics. 2008 Dec 15;24(24):2849-56
references: 18940824
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references: 12883005
references: RNA Biol. 2010 Jan-Feb;7(1):33-42
references: 20061798