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Review
. 2015;12(9):913-7.
doi: 10.1080/15476286.2015.1066956.

Group II intron lariat: Structural insights into the spliceosome

Affiliations
Review

Group II intron lariat: Structural insights into the spliceosome

Jessica K Peters et al. RNA Biol. 2015.

Abstract

Group II introns are self-splicing catalytic RNAs found in bacteria and the organelles of fungi and plants. They are thought to share a common ancestor with the spliceosome, which catalyzes the removal of nuclear introns from pre-mRNAs in eukaryotes. Recent structural and biochemical evidence supports the hypothesis that the spliceosome has a catalytic RNA core homologous to that found in group II introns. The crystal structure of a eukaryotic group IIB intron was recently determined and reveals the architecture of a branched lariat RNA that is also formed by the spliceosome. Here we describe the active site components of this intron and propose a model for RNA splicing involving dynamic base triples in the catalytic triad. Based on this structure, we draw analogies to the U2/U6 snRNA pairing and RNA-protein interactions that form in the active site of the spliceosome.

Keywords: RNA splicing; branch point; group II intron; lariat; spliceosome.

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Figures

Figure 1.
Figure 1.
Overall tertiary structure of P.li.LSUI2. (A) Interactions between DII and DVI. The two distal stems of DII (blue) coaxially stack and align parallel to DVI (purple). The two tetraloop-receptor interactions between domains II and VI, η-η′ and π-π′, are indicated with black boxes. Individual domains and subdomains are shown in different colors. (B) Arrangement of DV and DVI. DV (red) and DVI (purple) are oriented 180° relative to each other. The image on the left shows the 2 domains from the same angle as (A). The image on the right is rotated 90° about the y-axis to show that the 2 domains are not coaxially stacked. G1 is shown in green and interacts with A620.
Figure 2.
Figure 2.
P.li.LSUI2 core interactions and the proposed analogous spliceosomal residues. Coloring is consistent with the domains in Figure 1. P.li.LSUI2 residue numbers are shown in red, blue, and tan with proposed analogous U2 and U6 numbering in black. Spliceosomal numbering is from S. cerevisiae. In P.li.LSUI2, J2/3 residue A422 is disengaged from the catalytic triad (AGC) and instead forms a base triple with residues U549 and U584. Catalytic metals are shown as orange spheres and labeled M1 and M2.
Figure 3.
Figure 3.
Comparison of spliceosomal and group II intron core structures prior to the second step. Analogous residues are shown in the same color and the color scheme is from ref. 10. DV residues are shown in red, J2/3 in blue, J4/5 in tan, EBS1 in light blue, EBS3 in gray, ϵ in orange, ϵ′ in green, and γ′ in purple. The conserved branch point residue is circled in red. Dotted gray lines denote base triples, solid black lines designate base pairing, the dashed black line indicates the γ-γ′ base pair, and the thick black line represents the 2′-5′ bond between the branch point residue and the first residue of the intron. Numbering is as in Figure 2. (A) Predicted spliceosomal core elements. Numbering is according to the S. cerevisiae U2 and U6 sequences. The intron is shown as a thick gray line. (B) Group II intron core arrangement. Numbering is as in Figure 2.

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