This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The class I ligase ribozyme was generated de novo from random sequences. This catalytic RNA accelerates the attack of a small oligonucleotide's 3'OH on its own 5'-terminal triphosphate, yielding a 3'-5' phosphodiester linkage and pyrophosphate. We have generated variants of the ribozyme which are perform primer extension to produced a general polymerase ribozyme which can extend any template-primer pair, often by up to 14 nucleotides. In the RNA world hypothesis, this type of RNA-dependent RNA-polymerase activity would have been a critical component of the processes that led to the origins of life. Thus the class I ligase ribozyme is an extremely attractive target for crystallographic analysis in order to understand the structural basis for this primordial enzymology.
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