RNA catalyses nuclear pre-mRNA splicing

Sebastian M. Fica, Nicole Tuttle, Thaddeus Novak, Nan-Sheng Li, Jun Lu, Prakash Koodathingal, Qing Dai, Jonathan P. Staley () and Joseph A. Piccirilli ()
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Sebastian M. Fica: Graduate Program in Cell and Molecular Biology, The University of Chicago
Nicole Tuttle: 929 East 57th Street, The University of Chicago
Thaddeus Novak: Gordon Center for Integrative Science, 929 East 57th Street, The University of Chicago
Nan-Sheng Li: Gordon Center for Integrative Science, 929 East 57th Street, The University of Chicago
Jun Lu: 929 East 57th Street, The University of Chicago
Prakash Koodathingal: Cummings Life Sciences Center, 920 East 58th Street, The University of Chicago
Qing Dai: 929 East 57th Street, The University of Chicago
Jonathan P. Staley: Cummings Life Sciences Center, 920 East 58th Street, The University of Chicago
Joseph A. Piccirilli: 929 East 57th Street, The University of Chicago

Nature, 2013, vol. 503, issue 7475, 229-234

Abstract: Abstract In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a dynamic machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, after the discovery of self-splicing group II intron RNAs, the snRNAs were proposed to catalyse splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported so far. By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U6 snRNA catalyses both of the two splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Notably, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group II intron RNA. These findings indicate that group II introns and the spliceosome share common catalytic mechanisms and probably common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome.

Date: 2013
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DOI: 10.1038/nature12734

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