title: Evolutionary Origin and Conserved Structural Building Blocks of Riboswitches and Ribosomal RNAs: Riboswitches as Probable Target Sites for Aminoglycosides Interaction.
abstract: OBJECTIVE
  Riboswitches, as noncoding RNA sequences, control gene expression through direct ligand binding. Sporadic reports on the structural relation of riboswitches with ribosomal RNAs (rRNA), raises an interest in possible similarity between riboswitches and rRNAs evolutionary origins. Since aminoglycoside antibiotics affect microbial cells through binding to functional sites of the bacterial rRNA, finding any conformational and functional relation between riboswitches/rRNAs is utmost important in both of medicinal and basic research.
  
  
  METHODS
  Analysis of the riboswitches structures were carried out using bioinformatics and computational tools. The possible functional similarity of riboswitches with rRNAs was evaluated based on the affinity of paromomycin antibiotic (targeting "A site" of 16S rRNA) to riboswitches via docking method.
  
  
  RESULTS
  There was high structural similarity between riboswitches and rRNAs, but not any particular sequence based similarity between them was found. The building blocks including "hairpin loop containing UUU", "peptidyl transferase center conserved hairpin A loop"," helix 45" and "S2 (G8) hairpin" as high identical rRNA motifs were detected in all kinds of riboswitches. Surprisingly, binding energies of paromomycin with different riboswitches are considerably better than the binding energy of paromomycin with "16S rRNA A site". Therefore the high affinity of paromomycin to bind riboswitches in comparison with rRNA "A site" suggests a new insight about riboswitches as possible targets for aminoglycoside antibiotics.
  
  
  CONCLUSIONS
  These findings are considered as a possible supporting evidence for evolutionary origin of riboswitches/rRNAs and also their role in the exertion of antibiotics effects to design new drugs based on the concomitant effects via rRNA/riboswitches.
authors.affiliation: Drug Applied Research Center and Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Elnaz
authors.initials: E
authors.lastname: Mehdizadeh Aghdam
authors.affiliation: Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran. ; The School of Advanced Biomedical Sciences (SABS), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Barzegar
authors.affiliation: Drug Applied Research Center and Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. ; The School of Advanced Biomedical Sciences (SABS), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Saeid
authors.initials: MS
authors.lastname: Hejazi
keywords: Docking; Motif; Ribosomal RNA; Riboswitch; Structural similarity
references.citation: Bioinformatics. 2010 Nov 1;26(21):2689-97
references.pmid: 20929913
references.citation: Cell. 2009 Feb 20;136(4):615-28
references.pmid: 19239884
references.citation: Nucleic Acids Res. 2012 Feb;40(3):956-62
references.pmid: 21954438
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: J Med Chem. 2007 Aug 23;50(17):4096-104
references.pmid: 17665894
references.citation: Chem Biol. 2011 Mar 25;18(3):324-35
references.pmid: 21439477
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4899-903
references.pmid: 11296253
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Curr Opin Struct Biol. 2003 Jun;13(3):300-8
references.pmid: 12831880
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D182-4
references.pmid: 14681389
references.citation: Cell. 2013 Jan 17;152(1-2):68-81
references.pmid: 23332747
references.citation: Chem Rev. 2008 Apr;108(4):1171-224
references.pmid: 18361529
references.citation: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W260-5
references.pmid: 19483098
references.citation: Genome Biol. 2007;8(11):R239
references.pmid: 17997835
references.citation: Nucleic Acids Res. 2004 Apr 30;32(8):2342-52
references.pmid: 15121895
references.citation: Curr Opin Struct Biol. 2009 Jun;19(3):251-9
references.pmid: 19303767
references.citation: Genome Res. 2006 Jul;16(7):885-9
references.pmid: 16751343
references.citation: Cell. 1995 Jun 30;81(7):991-1002
references.pmid: 7541315
references.citation: Bioorg Med Chem Lett. 2004 Dec 6;14(23):5889-93
references.pmid: 15501063
references.citation: Q Rev Biophys. 2005 Aug;38(3):221-43
references.pmid: 16817983
references.citation: Trends Genet. 2000 Jun;16(6):276-7
references.pmid: 10827456
references.citation: Nat Rev Mol Cell Biol. 2004 Jun;5(6):451-63
references.pmid: 15173824
references.citation: Annu Rev Biophys. 2008;37:117-33
references.pmid: 18573075
references.citation: PLoS Pathog. 2010 Apr 22;6(4):e1000865
references.pmid: 20421948
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W19-24
references.pmid: 18502774
references.citation: Trends Biochem Sci. 2004 Jan;29(1):11-7
references.pmid: 14729327
references.citation: Biochim Biophys Acta. 2009 Sep-Oct;1789(9-10):592-611
references.pmid: 19619684
references.citation: Chem Biol. 2002 Sep;9(9):1043
references.pmid: 12323379
references.citation: RNA Biol. 2009 Apr-Jun;6(2):153-60
references.pmid: 19885993
references.citation: J Mol Graph Model. 2009 Aug;28(1):37-45
references.pmid: 19380244
references.citation: Curr Opin Microbiol. 2007 Apr;10(2):182-8
references.pmid: 17383223
references.citation: Cell. 2009 Feb 20;136(4):604-9
references.pmid: 19239882
references.citation: Science. 1996 Sep 20;273(5282):1678-85
references.pmid: 8781224
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W659-68
references.pmid: 17567620
references.citation: PLoS One. 2012;7(9):e45239
references.pmid: 23028870
references.citation: Bioinformatics. 2005 Sep 1;21 Suppl 2:ii47-53
references.pmid: 16204124
references.citation: Proc Natl Acad Sci U S A. 1990 Nov;87(21):8467-71
references.pmid: 2236056
references.citation: Angew Chem Int Ed Engl. 2004 Dec 10;43(48):6735-8
references.pmid: 15593140
references.citation: Nature. 1987 Jun 4-10;327(6121):389-94
references.pmid: 2953976
references.citation: Nucleic Acids Res. 2011 Oct;39(19):8586-98
references.pmid: 21745821
references.citation: RNA. 2008 Jan;14(1):89-97
references.pmid: 18000033
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D226-32
references.pmid: 23125362
references.citation: Cold Spring Harb Perspect Biol. 2012 Feb 01;4(2):
references.pmid: 21106649
references.citation: Angew Chem Int Ed Engl. 2010 Aug 16;49(35):6216-9
references.pmid: 20632338
references.citation: J Mol Graph Model. 2011 Sep;30:179-85
references.pmid: 21831681
references.citation: Chembiochem. 2007 Sep 24;8(14):1658-61
references.pmid: 17654628
references.citation: Nucleic Acids Res. 2010 Mar;38(4):1392-400
references.pmid: 19969538
references.citation: Crit Rev Biochem Mol Biol. 2006 Nov-Dec;41(6):329-38
references.pmid: 17092822
references.citation: Nucleic Acids Res. 2009 Jan;37(1):215-30
references.pmid: 19036788
references.citation: Science. 1996 Nov 22;274(5291):1367-71
references.pmid: 8910275
references.citation: Structure. 2001 Aug;9(8):647-58
references.pmid: 11587639