Group I catalytic intron

Group I catalytic introns are large self-splicing ribozymes. They catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of nine 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 open reading frames inserted in loop regions.

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 occupies 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 of 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, [cite journal | last = Steitz | first = TA | coauthors = Steitz JA | year = 1993 | title = A general two-metal-ion mechanism for catalytic RNA | journal = Proc Natl Acad Sci USA | volume = 90 | pages = 6498–6502 | pmid = 8341661 | doi = 10.1073/pnas.90.14.6498] which was unambiguously proven by a recently resolved high-resolution structure of the Azoarcus group I intron. [cite journal | last = Stahley | first = MR | coauthors = Strobel SA | year = 2006 | title = RNA splicing: group I intron crystal structures reveal the basis of splice site selection and metal ion catalysis | journal = Curr Opin Struct Biol | volume = 16 | pages = 319–326 | pmid = 16697179 | doi = 10.1016/j.sbi.2006.04.005]

Intron Folding

Since early 1990s, scientists started to study how the group I intron achieves its native structure in vitro, and some mechanisms of RNA folding have 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 in 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 elements display different potentials in entering the fast folding pathway. Meanwhile, cooperative assembly of the tertiary structure is important for the 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, 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 tRNAgenes in bacterial genomes, as well as in mitochondrial and chloroplastgenomes of lower eukaryotes, but only invade rRNA genes in the nuclear genome oflower eukaryotes. In higher plants, these introns seem to be restricted to a few
tRNA and mRNA genes of the chloroplasts and mitochondria. Both intron-earlyand 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 thewide spreading of the selfish group I introns. No biological role has beenidentified for group I introns thus far except for splicing of themselves from the precursorto 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] cite journal | last = Brion | first = P | coauthors = Westhof E | year = 1997 | title = Hierarchy and dynamics of RNA folding | journal = Annu Rev Biophys Biomol Struct | volume = 26 | pages = 113–137 | pmid = 9241415 | doi = 10.1146/annurev.biophys.26.1.113
* [4] cite journal | last = Cate | first = JH | coauthors = Gooding AR, Podell E, Zhou K, Golden BL, Kundrot CE, Cech TR, Doudna JA | year = 1996 | title = Crystal structure of a group I ribozyme domain: principles of RNA packing | journal = Science | volume = 273 | pages = 1678-1685 | pmid = 8781224 | doi = 10.1126/science.273.5282.1678
* [5] cite journal | last = Cech | first = TR | year = 1990 | title = Self-splicing of group I introns | journal = Annu Rev Biochem | volume = 59 | pages = 543–568 | pmid = 2197983 | doi = 10.1146/annurev.bi.59.070190.002551
* [6] cite journal | last = Chauhan | first = S | coauthors = Caliskan G, Briber RM, Perez-Salas U, Rangan P, Thirumalai D, Woodson SA | year = 2005 | title = RNA tertiary interactions mediate native collapse of a bacterial group I ribozyme | journal = J Mol Biol | volume = 353 | pages = 1199–1209 | pmid = 16214167 | doi = 10.1016/j.jmb.2005.09.015
* [7] cite journal | last = Haugen | first = P | coauthors = Simon DM and Bhattacharya D | year = 2005 | title = The natural history of group I introns | journal = TRENDS in Genetics | volume = 21 | pages = 111–119 | pmid = 15661357 | doi = 10.1016/j.tig.2004.12.007
* [8] cite journal | last = Rangan | first = P | coauthors = Masquida, B, Westhof E, Woodson SA | year = 2003 | title = Assembly of core helices and rapid tertiary folding of a small bacterial group I ribozyme | journal = Proc Natl Acad Sci USA | volume = 100 | pages = 1574–1579 | pmid = 12574513 | doi = 10.1073/pnas.0337743100
* [9] cite journal | last = Schroeder | first = R | coauthors = Barta A, Semrad K | year = 2004 | title = Strategies for RNA folding and assembly | journal = Nat Rev Mol Cell Biol | volume = 5 | pages = 908–919 | pmid = 15520810 | doi = 10.1038/nrm1497
* [10] cite journal | last = Thirumalai | first = D | coauthors = Lee N, Woodson SA, Klimov D | year = 2001 | title = Early events in RNA folding | journal = Annu Rev Phys Chem | volume = 52 | pages = 751–762 | pmid = 11326079 | doi = 10.1146/annurev.physchem.52.1.751
* [11] cite journal | last = Treiber | first = DK | coauthors = Williamson JR | year = 1999 | title = Exposing the kinetic traps in RNA folding | journal = Curr Opin Struct Biol | volume = 9 | pages = 339–345 | pmid = 10361090 | doi = 10.1016/S0959-440X(99)80045-1
* [12] cite journal | last = Xiao | first = M | coauthors = Leibowitz MJ, Zhang Y | year = 2003 | title = Concerted folding of a Candida ribozyme into the catalytically active structure posterior to a rapid RNA compaction | journal = Nucleic Acids Res | volume = 31 | pages = 3901–3908 | pmid = 12853605 | doi = 10.1093/nar/gkg455

External links

*Rfam|id=RF00028|name=Group I catalytic intron
* [http://www.rna.whu.edu.cn/gissd/ Group I Intron Sequence and Structure Database]