Importance of specific nucleotides in the folding of the natural form of the hairpin ribozyme

Biochemistry
Timothy J WilsonDavid M J Lilley

Abstract

The hairpin ribozyme in its natural context consists of two loops in RNA duplexes that are connected as arms of a four-way helical junction. Magnesium ions induce folding into the active conformation in which the two loops are in proximity. In this study, we have investigated nucleotides that are important to this folding process. We have analyzed the folding in terms of the cooperativity and apparent affinity for magnesium ions as a function of changes in base sequence and functional groups, using fluorescence resonance energy transfer. Our results suggest that the interaction between the loops is the sum of a number of component interactions. Some sequence variants such as A10U, G+1A, and C25U exhibit loss of cooperativity and reduced affinity of apparent magnesium ion binding. These variants are also very impaired in ribozyme cleavage activity. Nucleotides A10, G+1, and C25 thus appear to be essential in creating the conformational environment necessary for ion binding. The double variant G+1A/C25U exhibits a marked recovery of both folding and catalytic activity compared to either individual variant, consistent with the proposal of a triple-base interaction among A9, G+1, and C25 [Pinard, R., Lambert, D., Walter, N. G., Hec...Continue Reading

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Citations

May 28, 2005·Current Opinion in Structural Biology·David M J Lilley
Nov 30, 2002·Biochimie·Daniel A LafontaineDavid M J Lilley
May 23, 2002·RNA·Timothy J Wilson, David M J Lilley
Sep 11, 2012·Journal of the American Chemical Society·Stephanie Kath-SchorrDavid M J Lilley
Aug 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Asif IqbalDavid M J Lilley
Nov 15, 2001·The EMBO Journal·R PinardJ M Burke
Sep 29, 2009·Nucleic Acids Research·Kersten T Schroeder, David M J Lilley
Apr 8, 2006·RNA·Timothy J WilsonDavid M J Lilley
Jun 18, 2003·RNA·Sonya E MelcherDavid M J Lilley
Jan 20, 2004·RNA·Terry A GoodyDavid M J Lilley
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Elliot TanTaekjip Ha
Feb 1, 2014·Nucleic Acids Research·Lin Huang, David M J Lilley
Jul 21, 2014·Nature Chemical Biology·Yijin LiuDavid M J Lilley
Dec 8, 2006·Blood Cells, Molecules & Diseases·Timothy J WilsonDavid M J Lilley
Jun 18, 2004·Journal of Molecular Biology·Yaroslav I KuzminMartha J Fedor
Sep 5, 2006·Journal of Molecular Biology·Christopher I JonesPaul F Agris
Mar 25, 2011·Biochemical Society Transactions·David M J Lilley
Feb 1, 2013·RNA Biology·Peter DaldropDavid M J Lilley
Sep 7, 2011·Structure·Kersten T SchroederDavid M J Lilley
Jul 8, 2008·Journal of Molecular Biology·Ben Turner, David M J Lilley
May 7, 2016·Journal of the American Chemical Society·Timothy J WilsonDavid M J Lilley
Aug 11, 2016·Nanoscale·Lin Huang, David M J Lilley
Oct 6, 2016·The Journal of Physical Chemistry. B·Patrick O OchiengCharles G Hoogstraten
Mar 7, 2017·Nature Chemical Biology·Yijin LiuDavid M J Lilley
Dec 30, 2014·Nucleic Acids Research·Hui-Ting LeeSarah A Woodson
Jul 9, 2004·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Elizabeth R Sanchez, M Tyler Caudle
Jun 18, 2017·EMBO Reports·Lin HuangDavid Mj Lilley
Jun 18, 2017·Biochemical Society Transactions·David M J Lilley
Oct 14, 2003·The Journal of Biological Chemistry·Bruno SargueilJohn M Burke
Jun 11, 2020·Nucleic Acids Research·Lin HuangDavid M J Lilley
Jun 27, 2019·RNA Biology·Saira AshrafDavid M J Lilley
Aug 14, 2002·World Journal of Gastroenterology : WJG·Yue-Cheng YuYu-Ming Wang
Mar 14, 2007·The Journal of Biological Chemistry·Joseph W CottrellMartha J Fedor
Jan 10, 2003·The Journal of Biological Chemistry·Marc MeliMarie-Christine Maurel

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