Figure 7.

Model for the formation of intron circles. (A) Transesterification reactions catalyzed by the spliceosome. (F) Forward reactions, (R) reverse reactions (numbered 1–3). The arrows indicate the direction of nucleophilic attack. (F1) Attack of the BP 2′-OH on the phosphate (P) at the 5′ss. (F2) Attack of the 3′-OH at the end of E1 on the P at the 3′ss. (F3) Attack of the lariat tail 3′-OH on the BP P to form the intron circle. Below the pathway are spliceosome complexes within which these reactions occur. The active site of the C complex configuration has the 5′ss P and the BP 2′-OH in the active site for F1, whereas the C* complex configuration has the U2 BP helix pulled out of the active site to create the 3′ss binding site for F2. (ILS) Intron lariat spliceosome. The ILS is formed by spliced exon release (arrow) in the C* configuration (ILS•C*). For F3, it must remodel to the C configuration (ILS•C). (B) Cartoon showing remodeling of the RNA in the core of the ILS•C* complex to the proposed ILS•C complex and docking of the lariat tail for circularization. (C) Cartoon showing events leading to mixtures of processed and unprocessed full-length intron circles. Yellow spliceosomes represent ILS•C* complexes, and green spliceosomes represent ILS•C complexes. The nuclear exosome (purple) represents nuclear 3′ processing machinery interacting with ILS•C*, but it is not known which ILS forms permit processing. (Red) Intron, (green circles) 2′–5′ linkages, (green diamonds) 3′–5′ linkages. The lightning bolt indicates nucleophilic attack. The cartoons were made using ChimeraX as above.