With National Science Fund for distinguished young people (31525007\21625302),  Dr. Ming Lei for Medical School, Shanghai Jiaotong Univesity recently reported the 3.5-Å cryo-EM structures of Saccharomyces cerevisiae RNase P alone and in complex with pre-tRNAPhe. The results was published on Science as a research article.  Webpage of the paper can be found at the following site: http://science.sciencemag.org/content/early/2018/09/26/science.aat6678

Ribonuclease P (RNase P), one of only two universal ribozymes that have been found in organisms from all three domains of life, is responsible for the maturation of the 5′end of transfer RNA (tRNA). Bacterial RNase P contains a single small protein (Rpp) that is essential for substrate recognition and cleavage under physiological conditions. In contrast, archaeal and eukaryotic nuclear RNase Ps have evolved considerably more complex subunit compositions with an increased number of protein components. Unlike bacterial RNAs, the RNAs themselves in archaeal and eukaryotic RNase Ps are not generally catalytically active, and protein subunits are required to enhance the pre-tRNA substrate binding affinity and cleavage efficiency. However, very little is known about the structure of eukaryotic RNase Ps.

Dr. Lei's group has been the first to successfully present the 3.5-Å cryo-EM structures of S. cere-visiae nuclear RNase P holoenzyme alone and in complex with a pre-tRNA substrate. The structures unveil the arrange-ment and function of all the subunits within yeast RNase P and provide an integrated model depicting how the pre-tRNA substrate is recognized and how the hydrolysis of the 5′-leader of pre-tRNA is catalyzed by eukaryotic RNase P. Moreover, simulation analysis suggests a two-metal-ion SN2 reaction pathway of pre-tRNA cleavage. These results not only reveal the architecture of yeast RNase P but also provide a molecular basis of how the 5′-leader of pre-tRNA is processed by eukaryotic RNase P.

The Cryo-EM structures reported by Dr. Lei suggested that while bacterial RNase P RNA is catalytically active by itself, eukaryotic RNase P is a protein-controlled ribozyme – its protein components not only directly participate in substrate recognition, but also sta-bilize the catalytic RNA in a conformation optimal for pre-tRNA binding and cleavage reaction.