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. 1995 Mar 15;14(6):1276–1285. doi: 10.1002/j.1460-2075.1995.tb07111.x

Frequent use of the same tertiary motif by self-folding RNAs.

M Costa 1, F Michel 1
PMCID: PMC398207  PMID: 7720718

Abstract

We have identified an 11 nucleotide RNA motif, [CCUAAG...UAUGG], that is extraordinarily abundant in group I and group II self-splicing introns at sites known, or suspected from co-variation analysis, to interact with hairpin terminal loops with a GNRA consensus sequence. Base substitution experiments using a ribozyme-substrate system derived from a group I intron reveal that this motif interacts preferentially with GAAA terminal loops and binds them with remarkable affinity, compared with other known combinations of GNRA loops and matched targets. A copy of the [CCUAAG...UAUGG] motif which is present in domain I of many group II introns is shown to interact with the GAAA terminal loop that caps domain V. This is the first interaction to be identified between these two domains, whose mutual recognition is known to be necessary and sufficient for group II ribozymic activity. We conclude that interaction of [CCUAAG...UAUGG] with GAAA loops is one of the most common solutions used by nature to solve the problem of compacting and bringing together RNA structural domains.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bevilacqua P. C., Kierzek R., Johnson K. A., Turner D. H. Dynamics of ribozyme binding of substrate revealed by fluorescence-detected stopped-flow methods. Science. 1992 Nov 20;258(5086):1355–1358. doi: 10.1126/science.1455230. [DOI] [PubMed] [Google Scholar]
  2. Cech T. R., Damberger S. H., Gutell R. R. Representation of the secondary and tertiary structure of group I introns. Nat Struct Biol. 1994 May;1(5):273–280. doi: 10.1038/nsb0594-273. [DOI] [PubMed] [Google Scholar]
  3. Cech T. R. Self-splicing of group I introns. Annu Rev Biochem. 1990;59:543–568. doi: 10.1146/annurev.bi.59.070190.002551. [DOI] [PubMed] [Google Scholar]
  4. Chanfreau G., Jacquier A. Catalytic site components common to both splicing steps of a group II intron. Science. 1994 Nov 25;266(5189):1383–1387. doi: 10.1126/science.7973729. [DOI] [PubMed] [Google Scholar]
  5. Chanfreau G., Jacquier A. Interaction of intronic boundaries is required for the second splicing step efficiency of a group II intron. EMBO J. 1993 Dec 15;12(13):5173–5180. doi: 10.1002/j.1460-2075.1993.tb06212.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dichtl B., Pan T., DiRenzo A. B., Uhlenbeck O. C. Replacement of RNA hairpins by in vitro selected tetranucleotides. Nucleic Acids Res. 1993 Feb 11;21(3):531–535. doi: 10.1093/nar/21.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Doudna J. A., Cormack B. P., Szostak J. W. RNA structure, not sequence, determines the 5' splice-site specificity of a group I intron. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7402–7406. doi: 10.1073/pnas.86.19.7402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doudna J. A., Grosshans C., Gooding A., Kundrot C. E. Crystallization of ribozymes and small RNA motifs by a sparse matrix approach. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7829–7833. doi: 10.1073/pnas.90.16.7829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Herschlag D., Cech T. R. Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. Biochemistry. 1990 Nov 6;29(44):10159–10171. doi: 10.1021/bi00496a003. [DOI] [PubMed] [Google Scholar]
  10. Herschlag D. Evidence for processivity and two-step binding of the RNA substrate from studies of J1/2 mutants of the Tetrahymena ribozyme. Biochemistry. 1992 Feb 11;31(5):1386–1399. doi: 10.1021/bi00120a015. [DOI] [PubMed] [Google Scholar]
  11. Jacquier A., Jacquesson-Breuleux N. Splice site selection and role of the lariat in a group II intron. J Mol Biol. 1991 Jun 5;219(3):415–428. doi: 10.1016/0022-2836(91)90183-7. [DOI] [PubMed] [Google Scholar]
  12. Jacquier A., Michel F. Base-pairing interactions involving the 5' and 3'-terminal nucleotides of group II self-splicing introns. J Mol Biol. 1990 Jun 5;213(3):437–447. doi: 10.1016/S0022-2836(05)80206-2. [DOI] [PubMed] [Google Scholar]
  13. Jacquier A., Michel F. Multiple exon-binding sites in class II self-splicing introns. Cell. 1987 Jul 3;50(1):17–29. doi: 10.1016/0092-8674(87)90658-1. [DOI] [PubMed] [Google Scholar]
  14. Jaeger L., Michel F., Westhof E. Involvement of a GNRA tetraloop in long-range RNA tertiary interactions. J Mol Biol. 1994 Mar 11;236(5):1271–1276. doi: 10.1016/0022-2836(94)90055-8. [DOI] [PubMed] [Google Scholar]
  15. Jaeger L., Westhof E., Michel F. Function of P11, a tertiary base pairing in self-splicing introns of subgroup IA. J Mol Biol. 1991 Oct 20;221(4):1153–1164. doi: 10.1016/0022-2836(91)90925-v. [DOI] [PubMed] [Google Scholar]
  16. Jaeger L., Westhof E., Michel F. Monitoring of the cooperative unfolding of the sunY group I intron of bacteriophage T4. The active form of the sunY ribozyme is stabilized by multiple interactions with 3' terminal intron components. J Mol Biol. 1993 Nov 20;234(2):331–346. doi: 10.1006/jmbi.1993.1590. [DOI] [PubMed] [Google Scholar]
  17. James B. D., Olsen G. J., Liu J. S., Pace N. R. The secondary structure of ribonuclease P RNA, the catalytic element of a ribonucleoprotein enzyme. Cell. 1988 Jan 15;52(1):19–26. doi: 10.1016/0092-8674(88)90527-2. [DOI] [PubMed] [Google Scholar]
  18. Jarrell K. A., Dietrich R. C., Perlman P. S. Group II intron domain 5 facilitates a trans-splicing reaction. Mol Cell Biol. 1988 Jun;8(6):2361–2366. doi: 10.1128/mcb.8.6.2361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koch J. L., Boulanger S. C., Dib-Hajj S. D., Hebbar S. K., Perlman P. S. Group II introns deleted for multiple substructures retain self-splicing activity. Mol Cell Biol. 1992 May;12(5):1950–1958. doi: 10.1128/mcb.12.5.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Latham J. A., Cech T. R. Defining the inside and outside of a catalytic RNA molecule. Science. 1989 Jul 21;245(4915):276–282. doi: 10.1126/science.2501870. [DOI] [PubMed] [Google Scholar]
  21. Michel F., Jacquier A. Long-range intron-exon and intron-intron pairings involved in self-splicing of class II catalytic introns. Cold Spring Harb Symp Quant Biol. 1987;52:201–212. doi: 10.1101/sqb.1987.052.01.025. [DOI] [PubMed] [Google Scholar]
  22. Michel F., Jaeger L., Westhof E., Kuras R., Tihy F., Xu M. Q., Shub D. A. Activation of the catalytic core of a group I intron by a remote 3' splice junction. Genes Dev. 1992 Aug;6(8):1373–1385. doi: 10.1101/gad.6.8.1373. [DOI] [PubMed] [Google Scholar]
  23. Michel F., Umesono K., Ozeki H. Comparative and functional anatomy of group II catalytic introns--a review. Gene. 1989 Oct 15;82(1):5–30. doi: 10.1016/0378-1119(89)90026-7. [DOI] [PubMed] [Google Scholar]
  24. Michel F., Westhof E. Slippery substrates. Nat Struct Biol. 1994 Jan;1(1):5–7. doi: 10.1038/nsb0194-5. [DOI] [PubMed] [Google Scholar]
  25. Murphy F. L., Cech T. R. An independently folding domain of RNA tertiary structure within the Tetrahymena ribozyme. Biochemistry. 1993 May 25;32(20):5291–5300. doi: 10.1021/bi00071a003. [DOI] [PubMed] [Google Scholar]
  26. Murphy F. L., Cech T. R. GAAA tetraloop and conserved bulge stabilize tertiary structure of a group I intron domain. J Mol Biol. 1994 Feb 11;236(1):49–63. doi: 10.1006/jmbi.1994.1117. [DOI] [PubMed] [Google Scholar]
  27. Peebles C. L., Perlman P. S., Mecklenburg K. L., Petrillo M. L., Tabor J. H., Jarrell K. A., Cheng H. L. A self-splicing RNA excises an intron lariat. Cell. 1986 Jan 31;44(2):213–223. doi: 10.1016/0092-8674(86)90755-5. [DOI] [PubMed] [Google Scholar]
  28. Pley H. W., Flaherty K. M., McKay D. B. Model for an RNA tertiary interaction from the structure of an intermolecular complex between a GAAA tetraloop and an RNA helix. Nature. 1994 Nov 3;372(6501):111–113. doi: 10.1038/372111a0. [DOI] [PubMed] [Google Scholar]
  29. Pyle A. M., Green J. B. Building a kinetic framework for group II intron ribozyme activity: quantitation of interdomain binding and reaction rate. Biochemistry. 1994 Mar 8;33(9):2716–2725. doi: 10.1021/bi00175a047. [DOI] [PubMed] [Google Scholar]
  30. Reinhold-Hurek B., Shub D. A. Self-splicing introns in tRNA genes of widely divergent bacteria. Nature. 1992 May 14;357(6374):173–176. doi: 10.1038/357173a0. [DOI] [PubMed] [Google Scholar]
  31. SantaLucia J., Jr, Kierzek R., Turner D. H. Context dependence of hydrogen bond free energy revealed by substitutions in an RNA hairpin. Science. 1992 Apr 10;256(5054):217–219. doi: 10.1126/science.1373521. [DOI] [PubMed] [Google Scholar]
  32. Shub D. A., Gott J. M., Xu M. Q., Lang B. F., Michel F., Tomaschewski J., Pedersen-Lane J., Belfort M. Structural conservation among three homologous introns of bacteriophage T4 and the group I introns of eukaryotes. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1151–1155. doi: 10.1073/pnas.85.4.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Siegel V., Walter P. Binding sites of the 19-kDa and 68/72-kDa signal recognition particle (SRP) proteins on SRP RNA as determined in protein-RNA "footprinting". Proc Natl Acad Sci U S A. 1988 Mar;85(6):1801–1805. doi: 10.1073/pnas.85.6.1801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Strobel S. A., Cech T. R. Translocation of an RNA duplex on a ribozyme. Nat Struct Biol. 1994 Jan;1(1):13–17. doi: 10.1038/nsb0194-13. [DOI] [PubMed] [Google Scholar]
  35. Szewczak A. A., Moore P. B., Chang Y. L., Wool I. G. The conformation of the sarcin/ricin loop from 28S ribosomal RNA. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9581–9585. doi: 10.1073/pnas.90.20.9581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tuerk C., Gauss P., Thermes C., Groebe D. R., Gayle M., Guild N., Stormo G., d'Aubenton-Carafa Y., Uhlenbeck O. C., Tinoco I., Jr CUUCGG hairpins: extraordinarily stable RNA secondary structures associated with various biochemical processes. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1364–1368. doi: 10.1073/pnas.85.5.1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Woese C. R., Winker S., Gutell R. R. Architecture of ribosomal RNA: constraints on the sequence of "tetra-loops". Proc Natl Acad Sci U S A. 1990 Nov;87(21):8467–8471. doi: 10.1073/pnas.87.21.8467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van der Horst G., Christian A., Inoue T. Reconstitution of a group I intron self-splicing reaction with an activator RNA. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):184–188. doi: 10.1073/pnas.88.1.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. van der Veen R., Arnberg A. C., van der Horst G., Bonen L., Tabak H. F., Grivell L. A. Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro. Cell. 1986 Jan 31;44(2):225–234. doi: 10.1016/0092-8674(86)90756-7. [DOI] [PubMed] [Google Scholar]

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