title: Self-replication reactions dependent on tertiary interaction motifs in an RNA ligase ribozyme.
abstract: RNA can function both as an informational molecule and as a catalyst in living organisms. This duality is the premise of the RNA world hypothesis. However, one flaw in the hypothesis that RNA was the most essential molecule in primitive life is that no RNA self-replicating system has been found in nature. To verify whether RNA has the potential for self-replication, we constructed a new RNA self-assembling ribozyme that could have conducted an evolvable RNA self-replication reaction. The artificially designed, in vitro selected ligase ribozyme was employed as a prototype for a self-assembling ribozyme. The ribozyme is composed of two RNA fragments (form R1·Z1) that recognize another R1·Z1 molecule as their substrate and perform the high turnover ligation reaction via two RNA tertiary interaction motifs. Furthermore, the substrate recognition of R1·Z1 is tolerant of mutations, generating diversity in the corresponding RNA self-replicating network. Thus, we propose that our system implies the significance of RNA tertiary motifs in the early RNA molecular evolution of the RNA world.
authors.affiliation: Laboratory of Gene Biodynamics, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Ohmori
authors.forename: Hirohide
authors.initials: H
authors.lastname: Saito
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Ikawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Tan
authors.initials: T
authors.lastname: Inoue
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D019143:Evolution, Molecular; D007700:Kinetics; D008025:Ligases / Q000138:chemical synthesis / Q000737:chemistry*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D059370:RNA Folding; D016337:RNA, Catalytic / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D016337:RNA, Catalytic; D008025:Ligases
references.citation: Nucleic Acids Res. 2009 Feb;37(3):e23
references.pmid: 19136470
references.citation: RNA. 2001 Mar;7(3):395-404
references.pmid: 11333020
references.citation: Nat Struct Biol. 2001 Jul;8(7):580-2
references.pmid: 11427883
references.citation: Int J Biochem Cell Biol. 2009 Feb;41(2):254-65
references.pmid: 18775793
references.citation: Nature. 1996 Jul 25;382(6589):373-6
references.pmid: 8684470
references.citation: Methods. 2011 Jun;54(2):226-38
references.pmid: 21163353
references.citation: Chem Biol. 2004 Nov;11(11):1505-12
references.pmid: 15556001
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D182-4
references.pmid: 14681389
references.citation: Chem Biol. 2006 Aug;13(8):909-18
references.pmid: 16931340
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13750-5
references.pmid: 15365187
references.citation: Nucleic Acids Res. 2001 Jan 15;29(2):455-63
references.pmid: 11139616
references.citation: Nucleic Acids Res. 1999 Apr 15;27(8):1859-65
references.pmid: 10101194
references.citation: Cell. 1983 Dec;35(3 Pt 2):849-57
references.pmid: 6197186
references.citation: Nucleic Acids Res. 2008 Feb;36(2):520-31
references.pmid: 18048415
references.citation: Science. 2009 Feb 27;323(5918):1229-32
references.pmid: 19131595
references.citation: Nature. 1994 May 19;369(6477):221-4
references.pmid: 8183342
references.citation: Nucleic Acids Res. 2008 Mar;36(4):1138-52
references.pmid: 18158305
references.citation: J Biochem. 2001 Aug;130(2):251-5
references.pmid: 11481042
references.citation: RNA Biol. 2005 Oct-Dec;2(4):137-42
references.pmid: 17114929
references.citation: Biophys J. 2008 Oct;95(8):3892-905
references.pmid: 18621836
references.citation: Nature. 1996 May 2;381(6577):59-61
references.pmid: 8609988
references.citation: Angew Chem Int Ed Engl. 2008;47(44):8424-8
references.pmid: 18780409
references.citation: J Mol Biol. 1982 Nov 25;162(1):201-17
references.pmid: 6296405
references.citation: Science. 2011 Apr 8;332(6026):209-12
references.pmid: 21474753
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10505-10
references.pmid: 16024731
references.citation: Arch Biochem Biophys. 2009 Oct 15;490(2):163-70
references.pmid: 19728985
references.citation: Nucleic Acids Res. 1987 Feb 25;15(4):1699-715
references.pmid: 3822836
references.citation: J Biochem. 2003 Feb;133(2):189-95
references.pmid: 12761181
references.citation: J Mol Biol. 1993 Nov 20;234(2):331-46
references.pmid: 8230218
references.citation: Science. 1991 Mar 29;251(5001):1605-8
references.pmid: 1707185
references.citation: Biochemistry. 2003 Jul 29;42(29):8748-55
references.pmid: 12873135
references.citation: Science. 1992 Dec 18;258(5090):1910-5
references.pmid: 1470913
references.citation: RNA. 2007 Nov;13(11):2012-9
references.pmid: 17878321
references.citation: Nucleic Acids Res. 1996 Nov 15;24(22):4395-400
references.pmid: 8948629
references.citation: Cell. 1982 Nov;31(1):147-57
references.pmid: 6297745
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12733-40
references.pmid: 12239349
references.citation: J Mol Biol. 1984 Jun 25;176(2):279-306
references.pmid: 6205154
references.citation: Science. 1983 Feb 18;219(4586):859-62
references.pmid: 6186026
references.citation: FEBS Lett. 2009 Sep 3;583(17):2819-26
references.pmid: 19631647
references.citation: RNA. 2007 Jul;13(7):1017-26
references.pmid: 17586759
references.citation: Nat Chem. 2011 Jul 10;3(8):603-8
references.pmid: 21778979
references.citation: Nucleic Acids Res. 2009 Jan;37(1):215-30
references.pmid: 19036788