title: Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre.
abstract: RNA-structural elements play key roles in pre-mRNA splicing catalysis; yet, the formation of catalytically competent RNA structures requires the assistance of spliceosomal proteins. We show that the S. cerevisiae Cwc2 protein functions prior to step 1 of splicing, and it is not required for the Prp2-mediated spliceosome remodelling that generates the catalytically active B complex, suggesting that Cwc2 plays a more sophisticated role in the generation of a functional catalytic centre. In active spliceosomes, Cwc2 contacts catalytically important RNA elements, including the U6 internal stem-loop (ISL), and regions of U6 and the pre-mRNA intron near the 5' splice site, placing Cwc2 at/near the spliceosome's catalytic centre. These interactions are evolutionarily conserved, as shown by studies with Cwc2's human counterpart RBM22, indicating that Cwc2/RBM22-RNA contacts are functionally important. We propose that Cwc2 induces an active conformation of the spliceosome's catalytic RNA elements. Thus, the function of RNA-RNA tertiary interactions within group II introns, namely to induce an active conformation of domain V, may be fulfilled by proteins that contact the functionally analogous U6-ISL, within the spliceosome.
authors.affiliation: Department of Cellular Biochemistry, Max-Planck-Institute of Biophysical Chemistry, Göttingen, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rasche
authors.forename: Olexandr
authors.initials: O
authors.lastname: Dybkov
authors.forename: Jana
authors.initials: J
authors.lastname: Schmitzová
authors.forename: Berktan
authors.initials: B
authors.lastname: Akyildiz
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fabrizio
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lührmann
mesh_terms: D002384:Catalysis; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D012326:RNA Splicing; D012329:RNA, Bacterial / Q000235:genetics; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D017381:Spliceosomes / Q000235:genetics* / Q000378:metabolism*
chemical_list: C543031:Cwc2 protein, S cerevisiae; C516558:RBM22 protein, human; D012322:RNA Precursors; D022821:RNA Splice Sites; D012329:RNA, Bacterial; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C405486:U6 small nuclear RNA; C066490:PRP2 protein, S cerevisiae; D053487:DEAD-box RNA Helicases