title: Modular RNA architecture revealed by computational analysis of existing pseudoknots and ribosomal RNAs.
abstract: Modular architecture is a hallmark of RNA structures, implying structural, and possibly functional, similarity among existing RNAs. To systematically delineate the existence of smaller topologies within larger structures, we develop and apply an efficient RNA secondary structure comparison algorithm using a newly developed two-dimensional RNA graphical representation. Our survey of similarity among 14 pseudoknots and subtopologies within ribosomal RNAs (rRNAs) uncovers eight pairs of structurally related pseudoknots with non-random sequence matches and reveals modular units in rRNAs. Significantly, three structurally related pseudoknot pairs have functional similarities not previously known: one pair involves the 3' end of brome mosaic virus genomic RNA (PKB134) and the alternative hammerhead ribozyme pseudoknot (PKB173), both of which are replicase templates for viral RNA replication; the second pair involves structural elements for translation initiation and ribosome recruitment found in the viral internal ribosome entry site (PKB223) and the V4 domain of 18S rRNA (PKB205); the third pair involves 18S rRNA (PKB205) and viral tRNA-like pseudoknot (PKB134), which probably recruits ribosomes via structural mimicry and base complementarity. Additionally, we quantify the modularity of 16S and 23S rRNAs by showing that RNA motifs can be constructed from at least 210 building blocks. Interestingly, we find that the 5S rRNA and two tree modules within 16S and 23S rRNAs have similar topologies and tertiary shapes. These modules can be applied to design novel RNA motifs via build-up-like procedures for constructing sequences and folds.
authors.affiliation: Department of Physics, New York University 251 Mercer Street, New York, NY 10021, USA.
authors.forename: Samuela
authors.initials: S
authors.lastname: Pasquali
authors.forename: Hin Hark
authors.initials: HH
authors.lastname: Gan
authors.forename: Tamar
authors.initials: T
authors.lastname: Schlick
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D019295:Computational Biology; D003196:Computer Graphics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D016337:RNA, Catalytic / Q000737:chemistry; D012335:RNA, Ribosomal / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000737:chemistry; D012338:RNA, Ribosomal, 23S / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry
chemical_list: D016337:RNA, Catalytic; D012335:RNA, Ribosomal; D012336:RNA, Ribosomal, 16S; D012338:RNA, Ribosomal, 23S; D012367:RNA, Viral; C427204:hammerhead ribozyme; D012313:RNA
references.citation: Nucleic Acids Res. 2001 Oct 1;29(19):3928-38
references.pmid: 11574674
references.citation: RNA. 2001 Feb;7(2):266-74
references.pmid: 11233983
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):201-4
references.pmid: 10592225
references.citation: J Mol Biol. 2004 Aug 27;341(5):1129-44
references.pmid: 15321711
references.citation: Cell. 1988 Nov 4;55(3):447-58
references.pmid: 2846182
references.citation: Trends Biotechnol. 1994 Jul;12(7):268-75
references.pmid: 7519862
references.citation: Cell. 2001 Nov 30;107(5):679-88
references.pmid: 11733066
references.citation: Biopolymers. 1985 Aug;24(8):1437-47
references.pmid: 4041545
references.citation: J Chem Inf Comput Sci. 2001 May-Jun;41(3):550-60
references.pmid: 11410029
references.citation: J Mol Biol. 1996 Jul 26;260(4):479-83
references.pmid: 8759314
references.citation: Structure. 2002 Apr;10(4):527-34
references.pmid: 11937057
references.citation: Science. 2000 Aug 11;289(5481):905-20
references.pmid: 10937989
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1536-41
references.pmid: 10677496
references.citation: Nucleic Acids Res. 2003 Aug 15;31(16):4755-61
references.pmid: 12907716
references.citation: Nature. 2002 Jul 11;418(6894):222-8
references.pmid: 12110898
references.citation: J Mol Biol. 1998 Nov 27;284(2):205-25
references.pmid: 9813113
references.citation: Comput Appl Biosci. 1988 Mar;4(1):11-7
references.pmid: 3382986
references.citation: BMC Bioinformatics. 2004 Jul 6;5:88
references.pmid: 15238163
references.citation: Comput Appl Biosci. 1992 Jun;8(3):215-25
references.pmid: 1378772
references.citation: Biopolymers. 2004 Feb 15;73(3):340-7
references.pmid: 14755570
references.citation: Science. 1996 Aug 2;273(5275):595-603
references.pmid: 8662544
references.citation: Science. 2002 May 17;296(5571):1260-3
references.pmid: 12016301
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):175-6
references.pmid: 10592217
references.citation: Nat Struct Biol. 2000 Nov;7 Suppl:954-6
references.pmid: 11103998
references.citation: J Mol Biol. 1999 Nov 5;293(4):781-93
references.pmid: 10543967
references.citation: Nucleic Acids Res. 2000 Dec 1;28(23):4698-708
references.pmid: 11095680
references.citation: Nucleic Acids Res. 2003 Jun 1;31(11):2926-43
references.pmid: 12771219
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3429-31
references.pmid: 12824340
references.citation: Mol Cell Biol. 1999 Jan;19(1):567-76
references.pmid: 9858580
references.citation: J Mol Biol. 1994 Jan 14;235(2):508-31
references.pmid: 8289279
references.citation: Biophys Chem. 1996 Mar 7;59(1-2):179-84
references.pmid: 8867337
references.citation: J Mol Biol. 2004 Feb 20;336(3):607-24
references.pmid: 15095976
references.citation: J Mol Biol. 1999 Oct 22;293(2):271-81
references.pmid: 10550208
references.citation: Curr Biol. 2001 Sep 4;11(17):1369-73
references.pmid: 11553332
references.citation: J Virol. 2004 Apr;78(8):4003-10
references.pmid: 15047816
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3584-9
references.pmid: 10097080
references.citation: FEBS Lett. 1994 Oct 3;352(3):271-5
references.pmid: 7925985
references.citation: BMC Bioinformatics. 2002;3:2
references.pmid: 11869452
references.citation: Biopolymers. 1993 Sep;33(9):1389-404
references.pmid: 7691201
references.citation: Biophys J. 2002 Nov;83(5):2781-91
references.pmid: 12414710
references.citation: Nucleic Acids Res. 1989 Jun 26;17(12):4829-45
references.pmid: 2473442
references.citation: Bioinformatics. 2004 May 22;20(8):1285-91
references.pmid: 14962931
references.citation: Nature. 2000 Sep 21;407(6802):340-8
references.pmid: 11014183
references.citation: Comput Biomed Res. 1989 Oct;22(5):461-73
references.pmid: 2776449
references.citation: Nucleic Acids Res. 2001 Jan 1;29(1):228-9
references.pmid: 11125099
references.citation: Comput Appl Biosci. 1990 Oct;6(4):309-18
references.pmid: 1701685
references.citation: J Mol Biol. 1996 May 31;259(1):135-47
references.pmid: 8648641
references.citation: J Mol Biol. 1981 Mar 25;147(1):195-7
references.pmid: 7265238
references.citation: J Mol Biol. 1988 May 5;201(1):41-55
references.pmid: 3418699
references.citation: Curr Opin Biotechnol. 2002 Feb;13(1):31-9
references.pmid: 11849955
references.citation: Bioinformatics. 2003 Nov 22;19(17):2237-45
references.pmid: 14630652
references.citation: Virology. 1993 Jun;194(2):585-96
references.pmid: 8389075