Formation of a stalled early intermediate of pseudouridine synthesis monitored by real-time FRET.

RNA
Martin HengesbachMark Helm

Abstract

Pseudouridine is the most abundant of more than 100 chemically distinct natural ribonucleotide modifications. Its synthesis consists of an isomerization reaction of a uridine residue in the RNA chain and is catalyzed by pseudouridine synthases. The unusual reaction mechanism has become the object of renewed research effort, frequently involving replacement of the substrate uridines with 5-fluorouracil (f(5)U). f(5)U is known to be a potent inhibitor of pseudouridine synthase activity, but the effect varies among the target pseudouridine synthases. Derivatives of f(5)U have previously been detected, which are thought to be either hydrolysis products of covalent enzyme-RNA adducts, or isomerization intermediates. Here we describe the interaction of pseudouridine synthase 1 (Pus1p) with f(5)U-containing tRNA. The interaction described is specific to Pus1p and position 27 in the tRNA anticodon stem, but the enzyme neither forms a covalent adduct nor stalls at a previously identified reaction intermediate of f(5)U. The f(5)U27 residue, as analyzed by a DNAzyme-based assay using TLC and mass spectrometry, displayed physicochemical properties unaltered by the reversible interaction with Pus1p. Thus, Pus1p binds an f(5)U-containing sub...Continue Reading

References

Jan 1, 1994·Biochimie·J T KealeyD V Santi
Sep 28, 2000·Current Opinion in Chemical Biology·D M Lilley, T J Wilson
Nov 22, 2000·The Biochemical Journal·J Chen, J R Patton
Oct 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hu PanRobert M Stroud
Jan 20, 2004·RNA·Christopher J Spedaliere, Eugene G Mueller
Mar 3, 2004·Nucleic Acids Research·Kulwadee Phannachet, Raven H Huang
Mar 17, 2004·Journal of Molecular Biology·Mark Helm, Giuseppe Attardi
May 18, 2004·RNA·Xinliang Zhao, Yi-Tao Yu
Oct 8, 2004·Journal of the American Chemical Society·Christopher J SpedaliereEugene G Mueller
Dec 8, 2004·Archives of Biochemistry and Biophysics·Christopher S HamiltonEugene G Mueller
Oct 28, 2005·RNA·Wolfram C KurschatMark Helm
Apr 4, 2006·Biophysical Journal·Oana CobanG Ulrich Nienhaus
Sep 28, 2006·Biochemistry·Christopher S HamiltonEugene G Mueller
Oct 19, 2007·Journal of the American Chemical Society·Felix Voigts-HoffmannMark Helm
Oct 28, 2008·RNA·Priyatansh Gurha, Ramesh Gupta
May 30, 2009·Nature Structural & Molecular Biology·Bo LiangHong Li

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