LAUSR

Group II introns are extraordinarily versatile self-splicing ribozymes and retrotransposable elements widespread in bacteria and in bacterial-derived organelles (mitochondria and chloroplasts) of fungi, algae, plants, and of some early-branching metazoans (Zimmerly and Semper, 2015). These large and highly structured ribozymes have a conserved secondary structure organized into six domains (I to VI) and they recognize the flanking 5′ and 3′ exons through extensive Watson-Crick base-pairings between the intron “EBS” (Exon Binding Sites) and the exon “IBS” (Intron Binding Sites) sequences (Figure 1A). Despite their bacterial origin, it is now widely accepted that group II introns have been repurposed by natural evolution into the eukaryotic spliceosomal introns and the spliceosome (Toor et al., 2008; Costa et al., 2016; Galej et al., 2018). Both group II intron self-splicing and eukaryotic pre-mRNA splicing proceed through an identical pathway that involves two sequential transesterification reactions. First, a conserved “branchpoint” adenosine attacks the 5′ splice site generating a “lariat” intron intermediate with a 2′-5′ branch structure. During the second step, the terminal 3′OH group of the 5′ exon attacks the 3′ splice site leading to the ligation of the flanking exons and excision of the lariat intron. In bacteria, most group II introns encode a multifunctional reverse transcriptase (RT) and invade genomes through “retrohoming”, a highly site-specific mobility process operated both by the ribozyme and its encoded RT enzyme (Lambowitz and Zimmerly, 2011). Retrohoming is initiated by “reverse splicing”, a pathway during which the excised intron lariat, in complex with its RT, catalyzes its own insertion directly into a specific DNA target containing the ligated-exons sequence (Zimmerly et al., 1995). Natural group II introns are remarkably diverse regarding the structural organization of their ribozyme moiety, self-splicing pathways and the strategies they use to invade genomes. Here, I discuss recent findings regarding the splicing and mobility activities of group II introns that further emphasize the structural plasticity of these elements and their ability to be remodeled by molecular evolution into unique RNA-based machines, including the eukaryotic pre-mRNA splicing system.