Figure 1 -
The four different classes of introns. (a) group I introns. (b) group II introns. (c) Spliceosomal introns. (d) BHB introns. Only group I and II introns are autocatalytic. Adapted from Mukhopadhyay and Hausner (2021Mukhopadhyay J and Hausner G (2021) Organellar introns in fungi, algae, and plants. Cells 10:2001.), Lai et al. (2021Lai HC, Ho UY, James A, De Souza P and Roberts TL (2021) RNA metabolism and links to inflammatory regulation and disease. Cell Mol Life Sci 79:21.), Randau and Söll (2008Randau L and Söll D (2008) Transfer RNA genes in pieces. EMBO Rep 9:623-628.).
Figure 2 -
Occurrence of group I introns in different genomes and cellular compartments. The asterisks emphasize lineages within the tree of life that are notably rich in group I introns, encompassing fungi, plants, and red and green algae. In metazoans, group I introns have been found in non-bilaterian basal lineages (sponges, cnidarians, and placozoans) and in some species of sharks (Corsaro and Venditti, 2020Corsaro D and Venditti D (2020) Putative group I introns in the eukaryote nuclear internal transcribed spacers. Curr Genet 66:373-384.; Mukhopadhyay and Hausner, 2021Mukhopadhyay J and Hausner G (2021) Organellar introns in fungi, algae, and plants. Cells 10:2001.).
Figure 3 -
Generic representation of the group I intron structure with emphasis on key loops and domains featuring conserved sequences. Gray regions indicate unpaired segments (loops) that may contain Open Reading Frames (ORFs), which eventually harbor homing endonuclease genes (HEGs, shown in red). Orange rectangles show the location of conserved sequences P, Q, R, S, and IGS. Black rectangles represent exons located in the upstream and downstream regions of the 5’ and 3’ splice sites (green triangles), respectively. The binding site for exogenous guanine (ExoG) on the G-binding site, located in loop P7, is represented by an asterisk (adapted from Hausner et al., 2014Hausner G, Hafez M and Edgell DR (2014) Bacterial group I introns: Mobile RNA catalysts. Mob DNA 5: 8.).
Figure 4 -
Schematic representation of group I intron splicing. The splicing pathway involves two consecutive transesterification reactions. The first reaction is initiated by the 3’-OH group of an exogenous GTP (αG) that binds to the ωG-binding pocket located in the P7 region, and the 3’-OH group attacks the 5’ splice site. In the second reaction, the 3’-OH group of the released 5’ exon attacks the phosphodiester bond between the intron terminal G (ωG) and the 3’ exon, resulting in the release of the intron and the joining of the exons (adapted from Haugen et al., 2005Haugen P, Simon DM and Bhattacharya D (2005) The natural history of group I introns. Trends Genet 21:111-119.).
Figure 5 -
‘Homing’ process of a group I intron. In this DNA-based mobility pathway, the allele with IGI (shaded in blue) expresses an endonuclease (in beige). Cleavage at the recognition site of the endonuclease in the homologous allele without the intron causes DNA damage. The double-strand break (DSB) activates the cellular mechanism of homologous recombination repair, copying the intron and the endonuclease gene to the new site. Adapted from Barzel et al. (2011Barzel A, Privman E, Peeri M, Naor A, Shachar E, Burstein D, Lazary R, Gophna U, Pupko T and Kupiec M (2011) Native homing endonucleases can target conserved genes in humans and in animal models. Nucleic Acids Res 39:6646-6659.).
Figure 6 -
Molecules that inhibit group I intron splicing in vitro and their potential mechanisms of action. Streptomycin (von Ahsen and Schroeder, 1990von Ahsen U and Schroeder R (1990) Streptomycin and self-splicing. Nature 346:801., 1991von Ahsen U and Schroeder R (1991) Streptomycin inhibits splicing of group I introns by competition with the guanosine substrate. Nucleic Acids Res 19:2261-2265.), specific tuberactinomycins (Wank et al., 1994Wank H, Rogers J, Davies J and Schroeder R (1994) Peptide antibiotics of the tuberactinomycin family as inhibitors of group I intron RNA splicing. J Mol Biol 236:1001-1010.), certain pseudodisaccharides (Rogers and Davies, 1994Rogers J and Davies J (1994) The pseudodisaccharides: A novel class of group I intron splicing inhibitors. Nucleic Acids Res 22:4983-4988.), and L-arginine (Liu and Leibowitz, 1995Liu Y and Leibowitz MJ (1995) Bidirectional effectors of a group I intron ribozyme. Nucleic Acids Res 23:1284-1291.) competitively engage with the guanosine cofactor, while aminoglycosides such as neomycin B, tobramycin, gentamicin, 5-epi-sisomycin (von Ahsen et al., 1991von Ahsen U and Schroeder R (1991) Streptomycin inhibits splicing of group I introns by competition with the guanosine substrate. Nucleic Acids Res 19:2261-2265., 1992von Ahsen U, Davies J and Schroeder R (1992) Non-competitive inhibition of group I intron RNA self-splicing by aminoglycoside antibiotics. J Mol Biol 226:935-941.), along with pentamidine and tetracycline (Liu et al., 1994Liu Y, Tidwell RR and Leibowitz MJ (1994) Inhibition of in vitro splicing of a group I intron of Pneumocystis carinii. J Eukaryot Microbiol 41:31-38.), exhibit non-competitive inhibition but with a function not yet well elucidated (aminoglycosides likely interfere with the binding to ionic cofactors). Furthermore, modified small oligonucleotides inhibit auto-splicing by binding to precursor RNA specifically at the P7 site (Zhang et al., 2009Zhang L, Leibowitz MJ and Zhang Y (2009) Antisense oligonucleotides effectively inhibit the co-transcriptional splicing of a Candida group I intron in vitro and in vivo: Implications for antifungal therapeutics. FEBS Lett 583:734-738.; Disney et al., 2004Disney MD, Childs JL and Turner DH (2004) New approaches to targeting RNA with oligonucleotides: Inhibition of group I intron self-splicing. Biopolymers 73:151-161.). The 5-flucytosine is a base analog that, when incorporated into the intron, disrupts its folding (Mercure et al., 1993Mercure S, Montplaisir S and Lemay G (1993) Correlation between the presence of a self-splicing intron in the 25S rDNA of C. albicans and strains susceptibility to 5-fluorocytosine. Nucleic Acids Res 21:6020-6027.) and peptoids are synthetic oligomers, similar to peptides, designed to bind RNAs and disrupt their folding (Labuda et al., 2009Labuda LP, Pushechnikov A and Disney MD (2009) Small molecule microarrays of RNA-focused peptoids help identify inhibitors of a pathogenic group I intron. ACS Chem Biol 4:299-307. ). .
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