The exocyclic amine at the RNase P cleavage site contributes to substrate binding and catalysis

Journal of Molecular Biology
Ema KikovskaL A Kirsebom

Abstract

Most tRNAs carry a G at their 5' termini, i.e. at position +1. This position corresponds to the position immediately downstream of the site of cleavage in tRNA precursors. Here we studied RNase P RNA-mediated cleavage of substrates carrying substitutions/modifications at position +1 in the absence of the RNase P protein, C5, to investigate the role of G at the RNase P cleavage site. We present data suggesting that the exocyclic amine (2NH2) of G+1 contributes to cleavage site recognition, ground state binding and catalysis by affecting the rate of cleavage. This is in contrast to O6, N7 and 2'OH that are suggested to affect ground state binding and rate of cleavage to significantly lesser extent. We also provide evidence that the effects caused by the absence of 2NH2 at position +1 influenced the charge distribution and conceivably Mg2+ binding at the RNase P cleavage site. These findings are consistent with models where the 2NH2 at the cleavage site (when present) interacts with RNase P RNA and/or influences the positioning of Mg2+ in the vicinity of the cleavage site. Moreover, our data suggest that the presence of the base at +1 is not essential for cleavage but its presence suppresses miscleavage and dramatically increases ...Continue Reading

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Citations

Oct 7, 2008·Nature Structural & Molecular Biology·Richard Giegé
Feb 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ema KikovskaLeif A Kirsebom
Feb 21, 2016·Nucleic Acids Research·Nadia BrillanteRoland K Hartmann
Aug 28, 2007·Journal of Molecular Biology·Mathias BrännvallLeif A Kirsebom
Feb 27, 2009·IUBMB Life·Leif A Kirsebom, Stefan Trobro
Jan 27, 2010·Journal of Molecular Biology·William H McClainVenkat Gopalan

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