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Journal Article

Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre.

MPS-Authors
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Rasche,  N.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Dybkov,  O.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Schmitzova,  J.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Fabrizio,  P.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Lührmann,  R.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

1452580.pdf
(Publisher version), 2MB

Supplementary Material (public)

1452580_Sl.pdf
(Supplementary material), 3MB

Citation

Rasche, N., Dybkov, O., Schmitzova, J., Akyildiz, B., Fabrizio, P., & Lührmann, R. (2012). Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre. EMBO Journal, 31(6), 1591-1604. doi:10.1038/emboj.2011.502.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000F-8551-4
Abstract
RNA-structural elements play key roles in pre-mRNA splicing catalysis; yet, the formation of catalytically com- petent RNA structures requires the assistance of spliceo- somal 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, suggest- ing that Cwc2 plays a more sophisticated role in the generation of a functional catalytic centre. In active spli- ceosomes, Cwc2 contacts catalytically important RNA ele- ments, including the U6 internal stem-loop (ISL), and regions of U6 and the pre-mRNA intron near the 5 0 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 inter- actions 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.