Co-evolution of spliceosomal disassembly interologs: crowning J-protein component with moonlighting RNA-binding activity.

Spliceosome disassembly is catalyzed by the NineTeen-related (NTR) complex, which is constituted by several proteins, including Cwc23, Ntr1, and Ppr43. Cwc23 is an essential J-protein in Saccharomyces cerevisiae that recruits Ntr1, an NTC-related G-patch protein, to the spliceosome. Ntr1 interacts with Prp43, a DExD/H box RNA helicase protein, which facilitates the disassembly of spliceosomal intermediates. The interaction between Ntr1 and Prp43 is conserved and crucial for the disassembly process. However, the J-protein component of this complex is not studied in other eukaryotes. In silico analysis supported by results of yeast complementation and two-hybrid studies suggests that while Prp43 is highly conserved, both Ntr1 and Cwc23 are co-evolving components of the disassembly triad. The J-domain of Cwc23, which is otherwise dispensable for its function, is highly conserved, whereas the functionally critical C-terminus has significantly diverged in Cwc23 orthologs. Some eukaryotic orthologs of Cwc23 contain a distinct RNA recognition motif at their C-terminus and are able to bind RNA in vitro. Based on the results presented in this study, we propose that RNA-binding activity in some eukaryotic orthologs of Cwc23 might provide additional functional diversity or robustness to the J-protein/Hsp70 machine in spliceosomal remodelling processes.