Group I Introns and Their Maturases: Uninvited, but Welcome Guests

  • Mark G. Caprara
  • Richard B. Waring
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 16)


Homing endonucleases are a class of invasive genetic elements that use several elegant solutions to ensure their survival in natural populations. Like all successful mobile entities, homing endonucleases must either reduce the deleterious effects of insertion within essential genes of host genomes or be lost. Many homing endonuclease genes have solved this problem by colonizing self-splicing group I introns. This association makes homing endonuclease genes phenotypically “silent” since they are spliced out and thus absent from the mature mRNA of the invaded gene. Through this union, homing endonucleases and introns have co-evolved into a “hybrid” mobile element providing the introns with a mechanism to propagate themselves in a population. Remarkably, in some cases within fungal mitochondrial genomes, homing endonucleases have adapted to facilitate splicing of their encoding introns and contribute to the host’s regulation of the invaded gene. This novel adaptation, termed maturase activity, has likely served to ensure their fixture in mitochondrial and, perhaps, other genomes. In this chapter, we will review what is known concerning the mechanism of group I intron-encoded protein-assisted splicing. In addition, we will summarize new studies of both mobility and maturase functions that have resulted in a better understanding of how a single polypeptide carries out diverse and unrelated activities. Principles derived from maturase systems are likely to apply to numerous other multi-functional proteins that participate in diverse metabolic pathways.


Mitochondrial Genome Genetic Element Genetic Engineer Mobile Element Essential Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams PL, Stahley MR, Kosek AB, Wang J, Strobel SA (2004) Crystal structure of a self-splicing group I intron with both exons. Nature 430:45–50PubMedCrossRefGoogle Scholar
  2. Anziano PQ, Hanson DK, Mahler HR, Perlman PS (1982) Functional domains in introns: trans-acting and cis-acting regions of intron 4 of the cob gene. Cell 30:925–932PubMedCrossRefGoogle Scholar
  3. Banroques J, Delahodde A, Jacq C (1986) A mitochondrial RNA maturase gene transferred to the yeast nucleus can control mitochondrial mRNA splicing. Cell 46:837–844PubMedCrossRefGoogle Scholar
  4. Banroques J, Perea J, Jacq C (1987) Efficient splicing of two yeast mitochondrial introns controlled by a nuclear-encoded maturase. EMBO J 6:1085–1091PubMedGoogle Scholar
  5. Bassi GS, Weeks KM (2003) Kinetic and thermodynamic framework for assembly of the six-component bI3 group I intron ribonucleoprotein catalyst. Biochemistry 42:9980–9988PubMedCrossRefGoogle Scholar
  6. Bassi GS, de Oliveira DM, White MF, Weeks KM (2002) Recruitment of intron-encoded and co-opted proteins in splicing of the bI3 group I intron RNA. Proc Natl Acad Sci USA 99:128–133PubMedCrossRefGoogle Scholar
  7. Bousquet I, Dujardin G, Poyton RO, Slonimski PP (1990) Two group I mitochondrial introns in the cob-box and coxI genes require the same MRS1/PET157 nuclear gene product for splicing. Curr Genet 18:117–124PubMedCrossRefGoogle Scholar
  8. Bolduc JM, Spiegel PC, Chatterjee P, Brady KL, Downing ME, Caprara MG, Waring RB, Stoddard BL (2003) Structural and biochemical analyses of DNA and RNA binding by a bifunctional homing endonuclease and group I intron splicing factor. Genes Dev 17:2875–2888PubMedCrossRefGoogle Scholar
  9. Campisi DM, Calabro V, Frankel AD (2001) Structure-based design of a dimeric RNA-peptide complex. EMBO J 20:178–186PubMedCrossRefGoogle Scholar
  10. Cassiday LA, Maher LJ III (2002) Having it both ways: transcription factors that bind DNA and RNA. Nucleic Acids Res 30:4118–4126PubMedCrossRefGoogle Scholar
  11. Caprara MG, Mohr G, Lambowitz AM (1996a) A tyrosyl-tRNA synthetase protein induces tertiary folding of the group I intron catalytic core. J Mol Biol 257:512–531PubMedCrossRefGoogle Scholar
  12. Caprara MG, Lehnert V, Lambowitz AM, Westhof E (1996b) A tyrosyl-tRNA synthetase recognizes a conserved tRNA-like structural motif in the group I intron catalytic core. Cell 87:1135–1145PubMedCrossRefGoogle Scholar
  13. Cech TR (1990) Self-splicing of group I introns. Annu Rev Biochem 59:543–568PubMedCrossRefGoogle Scholar
  14. Chatterjee P, Brady KL, Solem A, Ho Y, Caprara MG (2003) Functionally distinct nucleic acid binding sites for a group I intron encoded RNA maturase/DNA homing endonuclease. J Mol Biol 329:239–251PubMedCrossRefGoogle Scholar
  15. Chevalier BS, Stoddard BL (2001) Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Nucleic Acids Res 29:3757–3774PubMedCrossRefGoogle Scholar
  16. Cho Y, Qiu YL, Kuhlman P, Palmer JD (1998) Explosive invasion of plant mitochondria by a group I intron. Proc Natl Acad Sci USA 95:14244–14249PubMedGoogle Scholar
  17. Dalgaard JZ, Klar AJ, Moser MJ, Holley WR, Chatterjee A, Mian IS (1997) Statistical modeling and analysis of the LAGLIDADG family of site-specific endonucleases and identification of an intein that encodes a site-specific endonuclease of the HNH family. Nucleic Acids Res 25:4626–4638PubMedCrossRefGoogle Scholar
  18. Delahodde A, Goguel V, Becam AM, Creusot F, Perea J, Banroques J, Jacq C (1989) Site-specific DNA endonuclease and RNA maturase activities of two homologous intron-encoded proteins from yeast mitochondria. Cell 56:431–441PubMedCrossRefGoogle Scholar
  19. De la Salle H, Jacq C, Slonimski PP (1982) Critical sequences within mitochondrial introns: pleiotropic mRNA maturase and cis-dominant signals of the box intron controlling reductase and oxidase. Cell 28:721–732Google Scholar
  20. Downing, M.E, Brady, K.L and Caprara M.G (2005). A C-terminal fragment of an intron-encoded maturase is sufficient for promoting group I intron splicing. RNA, 11:437–446.PubMedCrossRefGoogle Scholar
  21. Dujardin G, Jacq C, Slonimski PP (1982) Single base substitution in an intron of oxidase gene compensates splicing defects of the cytochrome b gene. Nature 298:628–632PubMedCrossRefGoogle Scholar
  22. Dujon B (1989) Group I introns as mobile genetic elements: facts and mechanistic speculations — a review. Gene 82:91–114PubMedGoogle Scholar
  23. Engelhardt MA, Doherty EA, Knitt DS, Doudna JA, Herschlag D (2000) The P5abc peripheral element facilitates preorganization of the Tetrahymena group I ribozyme for catalysis. Biochemistry 39:2639–2651PubMedCrossRefGoogle Scholar
  24. Geese WJ, Waring RB (2001) A comprehensive characterization of a group IB intron and its encoded maturase reveals that protein-assisted splicing requires an almost intact intron RNA. J Mol Biol 308:609–622PubMedCrossRefGoogle Scholar
  25. Geese WJ, Kwon YK, Wen X, Waring RB (2003) In vitro analysis of the relationship between endonuclease and maturase activities in the bi-functional group I intron-encoded protein, I-AniI. Eur J Biochem 270:1543–1554PubMedCrossRefGoogle Scholar
  26. Goddard MR, Burt A (1999) Recurrent invasion and extinction of a selfish gene. Proc Natl Acad Sci USA 96:13880–13885PubMedCrossRefGoogle Scholar
  27. Goguel V, Bailone A, Devoret R, Jacq C (1989) The bI4 RNA mitochondrial maturase of Saccharomyces cerevisiae can stimulate intra-chromosomal recombination in Escherichia coli. Mol Gen Genet 216:70–74PubMedCrossRefGoogle Scholar
  28. Goguel V, Delahodde A Jacq C (1992) Connections between RNA splicing and DNA intron mobility in yeast mitochondria: RNA maturase and DNA endonuclease switching experiments. Mol Cell Biol 12:696–705PubMedGoogle Scholar
  29. Golden BL, Gooding AR, Podell ER, Cech TR (1998) A preorganized active site in the crystal structure of the Tetrahymena ribozyme. Science 282:259–264PubMedGoogle Scholar
  30. Groudinsky O, Dujardin G, Slonimski PP (1981) Long range control circuits within mitochondria and between nucleus and mitochondria. II. Genetic and biochemical analyses of suppressors which selectively alleviate the mitochondrial intron mutations. Mol Gen Genet 184:493–503PubMedCrossRefGoogle Scholar
  31. Guo WW, Moran JV, Hoffman PW, Henke RM, Butow RA, Perlman PS (1995) The mobile group I intron 3α of the yeast mitochondrial COXI gene encoded a 35-kDa processed protein that is an endonuclease but not a maturase. J Biol Chem 270:15563–15570PubMedGoogle Scholar
  32. Henke RM, Butow RA, Perlman PS (1995) Maturase and endonuclease functions depend on separate conserved domains of the bifunctional protein encoded by the group I intron aI4α of yeast mitochondrial DNA. EMBO J 14:5094–5099PubMedGoogle Scholar
  33. Herbert CJ, Labouesse M, Dujardin G, Slonimski PP (1988) The NAM2 proteins from S. cerevisiae and S. douglasii are mitochondrial leucyl-tRNA synthetases, and are involved in mRNA splicing. EMBO J 7:473–483PubMedGoogle Scholar
  34. Ho Y, Waring RB (1999) The maturase encoded by a group I intron from Aspergillus nidulans stabilizes RNA tertiary structure and promotes rapid splicing. J Mol Biol 292:987–1001PubMedCrossRefGoogle Scholar
  35. Ho Y, Kim SJ, Waring RB (1997) A protein encoded by a group I intron in Aspergillus nidulans directly assists RNA splicing and is a DNA endonuclease. Proc Natl Acad Sci USA 94:8994–8999PubMedGoogle Scholar
  36. Jeffery CJ (1999) Moonlighting proteins. Trends Biochem Sci 24:8–11PubMedCrossRefGoogle Scholar
  37. Kreike J, Schulze M, Pillar T, Korte A, Rodel G (1986) Cloning of a nuclear gene MRS1 involved in the excision of a single group I intron (bI3) from the mitochondrial COB transcript in S. cerevisiae. Curr Genet 11:185–191PubMedCrossRefGoogle Scholar
  38. Labouesse M, Herbert CJ, Dujardin G, Slonimski PP (1987) Three suppressor mutations which cure a mitochondrial RNA maturase deficiency occur at the same codon in the open reading frame of the nuclear NAM2 gene. EMBO J 6:713–721PubMedGoogle Scholar
  39. Lambowitz AM, Belfort M (1993) Introns as mobile genetic elements. Annul Rev Biochem 62:587–622Google Scholar
  40. Lambowitz AM, Caprara MG, Zimmerly, S, Perlman PS (1999) Group I and group II ribozymes as RNPs: clues to the past and guides to the future. In: Gesteland RF, Atkins JF, Cech TR (eds) The RNA world II. Cold Spring Harbor Laboratory Press, New York, pp 451–485Google Scholar
  41. Lazowska J, Claude J, Slonimski PP (1980) Sequence of introns and flanking exons in wild-type and box3 mutants of cytochrome b reveals an interlaced splicing protein coded by an intron. Cell 22:333–348PubMedCrossRefGoogle Scholar
  42. Lazowska J, Claisse M, Gargouri A, Kotylak Z, Spyridakis A, Slonimski PP (1989) Protein encoded by the third intron of cytochrome b gene in Saccharomyces cerevisiae is an mRNA maturase. Analysis of mitochondrial mutants, RNA transcripts proteins and evolutionary relationships. J Mol Biol 205:275–289PubMedGoogle Scholar
  43. Lazowska J, Szczepanek T, Macadre C, Dokova M (1992) Two homologous mitochondrial introns from closely related Saccharomyces species differ by only a few amino acid replacements in their open reading frames: one is mobile, the other is not. CR Acad Sci III Sci Vie 315:37–41Google Scholar
  44. Lehnert V, Jaeger L, Michel F, Westhof E (1996) New loop-loop tertiary interactions in self-splicing introns of subgroup IC and ID: a complete 3D model of the Tetrahymena thermophila ribozyme. Chem Biol 12:993–1009Google Scholar
  45. Li G-Y, Becam A-M, Slonimski PP, Herbert CJ (1996) In vitro mutagenesis of the mitochondrial leucyl tRNA synthetase of Saccharomyces cerevisiae shows that the suppressor activity of the mutant proteins is related to the splicing function of the wild-type protein. Mol Gen Genet 252:667–675PubMedGoogle Scholar
  46. Merlos-Lange AM, Kanbay F, Zimmer M, Wolf K (1987). DNA splicing of mitochondrial group I and II introns in Schizosacchromyces pombe. Mol Gen Genet 206:273–278CrossRefGoogle Scholar
  47. Michel F, Westhof E (1990) Modelling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis. J Mol Biol 216:585–610PubMedCrossRefGoogle Scholar
  48. Pan J, Woodson SA (1999) The effect of long-range loop-loop interactions on folding of the Tetrahymena self-splicing RNA. J Mol Biol 294:955–965PubMedCrossRefGoogle Scholar
  49. Pellenz S, Harington A, Dujon B, Wolf K, Schaefer B (2002) Characterization of the I-SpomI endonuclease from fission yeast: insights into the evolution of a group I intron-encoded homing endonuclease. J Mol Evol 55:302–313PubMedCrossRefGoogle Scholar
  50. Rho SB, Martinis SA (2000) The bI4 group I intron binds directly to both its protein splicing partners, a tRNA synthetase and maturase, to facilitate RNA splicing activity. RNA 6:1882–1894PubMedCrossRefGoogle Scholar
  51. Rho SB, Lincecum TL Jr, Martinis SA (2002) An inserted region of leucyl-tRNA synthetase plays a critical role in group I intron splicing. EMBO J 21:6874–6881PubMedCrossRefGoogle Scholar
  52. Saldanha R, Ellington A, Lambowitz AM (1996) Analysis of the CYT-18 protein binding site at the junction of stacked helices in a group I intron RNA by quantitative binding assays and in vitro selection. J Mol Biol 261:23–42PubMedCrossRefGoogle Scholar
  53. Schafer B, Wilde B, Massardo DR, Manna F, Giudice LD, Wolf K (1994) A mitochondrial group I intron in fission yeast encodes a maturase and is mobile in crosses. Curr Genet 25:336–341PubMedGoogle Scholar
  54. Schroeder R, Grossberger R, Pichler A, Waldsich C (2002) RNA folding in vivo. Curr Opin Struct Biol 12:296–300PubMedCrossRefGoogle Scholar
  55. Solem A, Chatterjee P, Caprara MG (2002) A novel mechanism for protein-assisted group I intron splicing. RNA 8:412–425PubMedCrossRefGoogle Scholar
  56. Szczepanek T, Lazowska J (1996) Replacement of two non-adjacent amino acids in the S. cerevisiae bi2 intron-encoded RNA maturase is sufficient to gain a homing-endonuclease activity. EMBO J 15:3758–3767PubMedGoogle Scholar
  57. Szczepanek T, Jamoussi K, Lazowska J (2000). Critical base substitutions that affect the splicing and/or homing activities of the group I intron bi2 of yeast mitochondria. Mol Gen Genet 264:137–144PubMedGoogle Scholar
  58. Toor N, Zimmerly S (2002) Identification of a family of group II introns encoding LAGLIDADG ORFs typical of group I introns. RNA 8:1373–1377PubMedCrossRefGoogle Scholar
  59. Van Dyck L, Neupert W, Langer T (1998) The ATP-dependent PIM1 protease is required for the expression of intron-containing genes in mitochondria. Genes Dev 12:1515–1524PubMedGoogle Scholar
  60. Weeks KM, Cech TR (1995) Protein facilitation of group I intron splicing by assembly of the catalytic core and the 5′ splice site domain. Cell 82:221–230PubMedCrossRefGoogle Scholar
  61. Weeks KM, Cech TR (1996) Assembly of a ribonucleoprotein catalyst by tertiary structure capture. Science 271:345–348PubMedGoogle Scholar
  62. Weiss-Brummer B, Rodel G, Schweyen RJ, Kaudewitz F (1982). Expression of the split gene cob in yeast: evidence for a precursor of a „maturase“ protein translated from intron 4 and preceding exons. Cell 29:527–536PubMedCrossRefGoogle Scholar
  63. Wenzlau JM, Saldanha RJ, Butow RA, Perlman PS (1989) A latent intron-encoded maturase is also an endonuclease needed for intron mobility. Cell 56:421–430PubMedCrossRefGoogle Scholar
  64. Woodson SA (2000) Recent insights on RNA folding mechanisms from catalytic RNA. Cell Mol Life Sci 57:796–808PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Mark G. Caprara
    • 1
  • Richard B. Waring
    • 2
  1. 1.Center for RNA Molecular BiologyCase Western Reserve University School of MedicineClevelandUSA
  2. 2.Department of BiologyTemple UniversityPhiladelphiaUSA

Personalised recommendations