Abstract
It is known that tRNAs play an essential role in genetic information transfer from DNA to protein. The maturation of tRNA precursors is performed by the endoribonuclease RNase P, which classically consists of a main RNA segment and accessory proteins. However, the newly identified human mitochondrial RNase P-like protein (MRPP123) complex is unique in that it is composed of three proteins without RNA. Here, we determined the crystal structure of MRPP123 complex subunit 3 (MRPP3), which is thought to carry out the catalytic reaction. A detailed structural analysis in combination with biochemical assays suggests that MRPP3 is in an auto-inhibitory conformation in which metal ions that are essential for catalysis are excluded from the active site. Our results indicate that further regulation is necessary to rearrange the conformation of the active site of MRPP3 and trigger it, thus providing important information to understand the activation of MRPP123.