STRUCTURAL STUDIES OF FUNCTIONAL RNA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The discovery of the RNA self-splicing group I intron provided the first direct evidence that not all enzymes are proteins. Additionally, it has been found that a group of RNAs called riboswitches can regulate gene expression. One focus in our laboratory is the determination of crystal structures of these RNAs. We recently reported crystal structures of several group I intron splicing intermediates in states related to the exon ligation reaction, and are now undertaking structural studies to characterize the complete splicing pathway of this intron by targeting the first step of splicing and post splicing reactions. Additionally, we have also solved the structure of the GlmS ribozyme bound to its native ligand, glucosamine-6-phosphate. We are now working towards the first structures of the GEMM and glycine riboswitches. The glycine riboswitch contains two aptamers that respond cooperativity to changes in glycine concentration. The GEMM riboswitch is the first example of an RNA that is involved in cell signaling, as it binds a second messenger signaling molecule, cyclic bis(3'-5')diguanylic acid (c-diGMP). This project focuses on the group I self-splicing intron along with the GEMM and glycine riboswitches.