Group I catalytic intron

Group I catalytic introns are large self-splicing ribozymes. They catalyse their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of 9 paired regions (P1-P9). These fold to essentially two domains - the P4-P6 domain (formed from the stacking of P5, P4, P6 and P6a helices) and the P3-P9 domain (formed from the P8, P3, P7 and P9 helices). The secondary structure mark-up for this family represents only this conserved core. Group I catalytic introns often have long ORFs inserted in loop regions.

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Catalysis

Splicing of group I introns is processed by two sequential ester-transfer reactions. The exogenous guanosine or guanosine nucleotide (exoG) first docks onto the active G-binding site located in P7, and its 3'-OH is aligned to attack the phosphorester bond at the 5' splice site located in P1, resulting in a free 3'-OH group at the upstream exon and the exoG being attached to the 5' end of the intron. Then the terminal G (omega G) of the intron swaps the exoG and occupy the G-binding site to organize the second ester-transfer reaction, the 3' OH group of the upstream exon in P1 is aligned to attacks the 3' splice site in P10, leading to the ligation the adjacent upstream and downstream exons and free of the catalytic intron.

Two-metal-ion mechanism seen in protein polymerases and phosphatases was proposed to be used by group I and group II introns to process the phosphoryl transfer reactions,^[1] which was unambiguously proven by a recently resolved high-resolution structure of the Azoarcus group I intron.^[2]

Intron Folding

Since early 1990s, the community started to study how group I intron achieves its native structure in vitro, and some mechanisms of RNA folding has been appreciated thus far. It is agreed that the tertiary structure is folded after the formation of the secondary structure. During folding, RNA molecules are rapidly populated into different folding intermediates, the intermediates containing native interactions are further folded into the native structure through a fast folding pathway, while those containing non-native interactions are trapped metastable or stable non-native conformations, and the process of conversion to the native structure occurs very slowly. It is evident that group I introns differing in the set of peripheral element display different potentials in entering the fast folding pathway. Meanwhile, cooperative assembly of the tertiary structure is important for folding of the native structure. Nevertheless, folding of group I introns in vitro encounters both thermodynamic and kinetic challenges. A few RNA binding proteins and chaperones have been shown to promote the folding of group I introns in vitro and in bacteria by stabilizing the native intermediates or structure, and by destabilizing the non-native structures, respectively.

Distribution, Phylogeny and Mobility

Group I introns are distributed in bacteria, lower eukaryotes and higher plants. However, their occurrence in bacteria seems to be more sporadic than in lower eukaryotes, and they have become prevalent in higher plants. The genes that group I introns interrupt differ significantly: They interrupt rRNA, mRNA and tRNA genes in bacterial genomes, as well as in mitochondrial and chloroplast genomes of lower eukaryotes, but only invade rRNA genes in the nuclear genome of lower eukaryotes. In higher plants, these introns seem to be restricted to a few tRNA and mRNA genes of the chloroplasts and mitochondria. Both intron-early and intron-late theories have found evidences in explaining the origin of group I introns. Some group I introns encode homing endonuclease (HEG), which catalyzes intron mobility. It is proposed that HEGs move the intron from one location to another, from one organism to another and thus account for the wide spreading of the selfish group I introns. No biological role has been identified for group I introns thus far except for splicing of themselves from the precursor to prevent the death of the host that they live by. A small number of group I introns are also found to encode a class of proteins called maturases that facilitate the intron splicing.

References

• [3] Brion, P; Westhof E (1997). "Hierarchy and dynamics of RNA folding". Annu Rev Biophys Biomol Struct 26: 113–137. PMID 9241415.
• [4] Cate, JH; Gooding AR, Podell E, Zhou K, Golden BL, Kundrot CE, Cech TR, Doudna JA (1996). "Crystal structure of a group I ribozyme domain: principles of RNA packing". Science 273: 1678–1685. PMID 8781224.
• [5] Cech, TR (1990). "Self-splicing of group I introns". Annu Rev Biochem 59: 543–568. PMID 2197983.
• [6] Chauhan, S; Caliskan G, Briber RM, Perez-Salas U, Rangan P, Thirumalai D, Woodson SA (2005). "RNA tertiary interactions mediate native collapse of a bacterial group I ribozyme". J Mol Biol 353: 1199–1209. PMID 16214167.
• [7] Haugen, P; Simon DM and Bhattacharya D (2005). "The natural history of group I introns". TRENDS in Genetics 21: 111–119. PMID 15661357.
• [8] Rangan, P; Masquida, B, Westhof E, Woodson SA (2003). "Assembly of core helices and rapid tertiary folding of a small bacterial group I ribozyme". Proc Natl Acad Sci USA 100: 1574–1579. PMID 12574513.
• [9] Schroeder, R; Barta A, Semrad K (2004). "Strategies for RNA folding and assembly". Nat Rev Mol Cell Biol 5: 908–919. PMID 15520810.
• [10] Thirumalai, D; Lee N, Woodson SA, Klimov D (2001). "Early events in RNA folding". Annu Rev Phys Chem 52: 751–762. PMID 11326079.
• [11] Treiber, DK; Williamson JR (1999). "Exposing the kinetic traps in RNA folding". Curr Opin Struct Biol 9: 339–345. PMID 10361090.
• [12] Xiao, M; Leibowitz MJ, Zhang Y (2003). "Concerted folding of a Candida ribozyme into the catalytically active structure posterior to a rapid RNA compaction". Nucleic Acids Res 31: 3901–3908. PMID 12853605.