The Structural and Functional Uniqueness of the glmS Ribozyme - Progress in Molecular Biology and Translational Science - page 171

2. THE glmS RIBOSWITCH/RIBOZYME
The discovery of ribozymes over 30 years ago changed the way sci-
entists think about biological catalysis, and the discovery of riboswitches
many years later further advanced the understanding of the complexity of
RNA functions in the cell. The structural and functional details of each ribo-
zyme and riboswitch have been extensively explored using biochemical and
biophysical methods, resulting in a vast accumulation of basic knowledge to
facilitate the utilization of these functional RNAs for the betterment of
human health. RNA biology became increasingly interesting when the glmS
riboswitch was discovered in 2004 by Breaker and colleagues, with the
exciting development that this riboswitch is also a ribozyme. 2 This discovery
was just the beginning of a number of studies that continue to show the
uniqueness of this RNA. This review will highlight the details of this small,
self-cleaving, uniquely coenzyme-dependent ribozyme.
The glmS riboswitch stands out among the classes of riboswitches as the
only member with intrinsic catalytic capability. The criteria to establish
riboswitch function are (1) the RNA must specifically bind a metabolite,
(2) the RNA exhibits conformational change induced by metabolite bind-
ing, and (3) the RNA influences gene expression in a metabolite-dependent
manner. 3,4 In the presence of the amine-containing sugar glucosamine-6-
phosphate (GlcN6P), the glmS riboswitch/ribozyme undergoes self-
cleavage, which sets this riboswitch apart from other riboswitch classes that
influence gene expression largely through transcription termination or inhi-
bition of translation initiation. The criterion for influencing gene expression
is fulfilled by glmS riboswitch self-cleavage, after which the associated mes-
senger RNA is further targeted for degradation. 5 The glmS riboswitch/ribo-
zyme has also been shown to control expression of b -galactosidase
production when placed upstream of the reporter gene open reading frame. 2
The glmS ribozyme stands out among the classes of natural RNA catalysts
as the only ribozyme requiring a coenzyme for activity. 2,6 The GlcN6P
coenzyme plays a direct role in the catalytic mechanism of RNA self-
cleavage, 6 whereas other RNA catalyst may require exogenous compounds
as cosubstrates or allosteric effectors. A notable example is the group I intron
that utilizes exogenous guanosine as a substrate but not a catalyst per se of the
splicing mechanism. Both biochemical and biophysical methods have been