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ISBN: 978-83-60043-10-3 - eurobic9

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Eurobic9, 2-6 September, 2008, Wrocław, Poland<br />

PL<strong>10</strong>. Specific Keys to Success for Ribozymes and Riboswitches: Metal Ions<br />

and Metal Ion Complexes<br />

R.K.O. Sigel<br />

Institute of Inorganic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland,<br />

e-mail: roland.sigel@aci.uzh.ch<br />

RNAs are involved in many processes within living cells, ribozymes and riboswitches being only two examples<br />

of functional RNAs. Ribozymes perform catalytic reactions, whereas riboswitches are involved in the regulation<br />

of gene expression by specifically binding small metabolites. Our research focuses on the self-splicing group II<br />

intron ribozyme Sc.ai5γ and two riboswitches responsive to either coenzyme B12 or Mg 2+ (Figure).<br />

Like most group II introns, Sc.ai5γ is highly dependent on Mg 2+ and very sensitive to the presence of other M n+<br />

ions [1]: Ca 2+ inhibits splicing already at very low concentrations. By a combination of biochemical [1b], NMR<br />

[2] and single molecule FRET experiments [3] we are now investigating the origin of Ca 2+ inhibition by<br />

characterizing the intrinsic metal ion binding properties of these large RNAs and the effect of different M n+ ions<br />

on catalysis, local structures and folding.<br />

The btuB riboswitch from E. coli regulates the expression of a B12 transport protein and thus the uptake of B12<br />

into the cell. We could recently show that the corrin moiety is responsible for the structural change of the<br />

riboswitch, whereas the axial ligands of B12 regulate the affinity towards the RNA [4]. We are currently<br />

extending these studies by investigating the role of the corrin side chains on the riboswitch structure.<br />

Acknowledgement: Financial support by the Swiss Nat. Sci. Found. (SNF-Förderungsprofessur PP002-114759<br />

and project 200021-117999) is gratefully acknowledged.<br />

References:<br />

[1] a) R.K.O. Sigel, Eur. J. Inorg. Chem., 2281 (2005). b) M.C. Erat, R.K.O. Sigel, J. Biol. Inorg. Chem., 13, doi<br />

<strong>10</strong>.<strong>10</strong>07/s00775-008-0390-7 (2008). c) E. Freisinger, R.K.O. Sigel, Coord. Chem. Rev., 251, 1<strong>83</strong>4 (2007).<br />

[2] a) M.C. Erat, O. Zerbe, T. Fox, R.K.O. Sigel, ChemBioChem, 8, 306 (2007). b) M.C. Erat, R.K.O. Sigel,<br />

Inorg. Chem., 46, 11224 (2007).<br />

[3] M. Steiner, D. Rueda, R.K.O. Sigel, submitted for publication.<br />

[4] S. Gallo, M. Oberhuber, R.K.O. Sigel, B. Kräutler, ChemBioChem, 9, 1408 (2008).<br />

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