In 1985 I received the Pfizer Award for my group’s discovery of a catalytic RNA molecule in the ciliated protozoan, <i>Tetrahymena</i>. At that time, we understood the chemistry that was catalyzed by this “ribozyme,” and we subsequently applied the tools of mechanistic enzymology to characterize the elemental steps of the reaction in depth. Our attention then turned to the structure of the ribozyme, which we eventually solved by x-ray crystallography. The next enzyme studied in my lab was telomerase, a ribonucleoprotein (RNP) enzyme. Its RNA subunit had been discovered by Carol Greider and Liz Blackburn, and in 1997 Joachim Lingner in my lab discovered its catalytic protein subunit, TERT (Telomerase Reverse Transcriptase). The chemistry and regulation of this RNP enzyme would dominate the next two decades of my laboratory’s efforts. Since 2013, Chen Davidovich and others in the group turned our attention to Polycomb Repressive Complex 2 (PRC2), a histone methyltransferase that epigenetically silences gene expression. Because it is regulated by DNA sequence, pre-existing methyl groups on histones, and RNA, it is the most complex enzyme we have studied.

Tales of three enzymes: RNA, RNP, and protein

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.