Uniformity amid diversity in RNase P

Abstract

The ribonucleoprotein RNase P, which catalyzes the Mg2+-dependent removal of the 5′ leader sequence in all precursor tRNAs (ptRNAs), is remarkable for the diversity in its subunit composition (Fig. 1 A). Although all RNase P holoenzymes have an essential RNA subunit, the number of protein subunits varies from 1 in Bacteria to at least 4 in Archaea and 9–10 in Eukarya (1–5). The finding that the bacterial RNase P RNA (RPR) subunit alone is catalytic under in vitro conditions of high ionic strength provided one of the first examples of a true cellular RNA enzyme (6). Despite a shared ancestry, as reflected by sequence/structure similarities especially in regions expected to comprise the catalytic core (Fig. 1 B–E), to date, only some archaeal RPRs were proven to be weakly catalytic, whereas all eukaryal RPRs examined were inactive in the absence of their cognate RNase P proteins (Rpps; refs. 1, 3, 7, and 8). Consistent with the RNA world hypothesis, these findings suggest that the primordial ribozyme activity observed in bacterial RPRs was somehow lost in many archaeal and all eukaryal RPRs with concomitant gains by their cognate Rpps that might have usurped the RPR's catalytic roles. However, such a postulate can now be laid to rest because in this issue of PNAS, Kikovska et al. (9) provide evidence that human RPR can catalyze processing of four different ptRNAs and a model substrate, albeit at rates much lower than that of bacterial RPR.