You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Use of a coenzyme by the glmS ribozymeriboswitch suggests primordial expansion of RNA chemistry by small molecules
Contributor:
Ferré-D'Amaré, Adrian R.
Published:
The Royal Society, 2011
Published in:
Philosophical Transactions: Biological Sciences, 366 (2011) 1580, Seite 2942-2948
Language:
English
ISSN:
0962-8436
Origination:
Footnote:
Description:
The glmS ribozyme-riboswitch is the first known example of a naturally occurring catalytic RNA that employs a small molecule as a coenzyme. Binding of glucosamine-6-phosphate (GlcN6P) activates self-cleavage of the bacterial ribozyme, which is part of the mRNA encoding the metabolic enzyme GlcN6P-synthetase. Cleavage leads to negative feedback regulation. GlcN6P binds in the active site of the ribozyme, where its amine could function as a general acid and electrostatic catalyst. The ribozyme is pre-folded but inactive in the absence of GlcN6P, demonstrating it has evolved strict dependence on the exogenous small molecule. The ribozyme showcases the ability of RNA to co-opt non-covalently bound small molecules to expand its chemical repertoire. Analogue studies demonstrate that some molecules other than GlcN6P, such as L-serine (but not D-serine), can function as weak activators. This suggests how coenzyme use by RNA world ribozymes may have led to evolution of proteins. Primordial cofactor-dependent ribozymes may have evolved to bind their cofactors covalently. If amino acids were used as cofactors, this could have driven the evolution of RNA aminoacylation. The ability to make covalently bound peptide coenzymes may have further increased the fitness of such primordial ribozymes, providing a selective pressure for the invention of translation.