Ribonuclease P is clearly one of the most ancient surviving ribozymes from the hypothetical, pre-biotic “RNA World”. In every kingdom of life, a form of RNase P has survived that has an essential, catalytic RNA subunit. Two questions arise from this remarkable retention of RNA-based catalysis:  why has the function been retained as an RNA catalyst, rather than being taken over by protein as with other enzyme functions, and  why have the archaeal and eukaryotic nuclear enzymes become such complex ribonucleoproteins?
The answer to the first question might be fundamentally similar to why the other ancient ribozyme, the ribosome, has been conserved. Both catalytic RNAs were developed to recognize a large number of tRNAs that are distinct, in that they must bring different amino acids, yet have key conserved features that allow them to be recognized as “tRNA.” The need to specifically recognize all “tRNA” structures and not other RNA structures, leaves very little tolerance. Once a ribozyme existed that was able to do this, the selection pressure for keeping the function within the ribozyme, rather than developing a new protein-based enzyme, would be very strong. Although RNase P could develop limited tolerance for additional substrates, or even develop a related enzyme to deal with additional substrates (e.g. RNase MRP), the core substrate recognition could not stray substantially.
The cleavage of pre-tRNAs by the eukaryotic RNase P appears to have slightly different determinants from that of the bacterial enzymes. The human enzyme does not cleave the same minimal substrates as the bacterial ribozyme, requiring an additional loop between the acceptor stem and T stem-loop domains (Yuan and Altman, 1995
). The yeast enzyme has been shown to interact with pre-tRNAs within the 3′ trailer regions as well as the tRNA domain and the enzyme binds to, and is strongly inhibited by, single-stranded homoribopolymers [poly(G) and poly(U) > poly(A)
poly(C)] (Ziehler et al., 2000
The large increase in the number and size of the protein subunits could have multiple causes. First, the proteins might provide additional opportunities for recognition of RNA or ribonucleoprotein substrates. As noted above, pre-tRNA cleavage by nuclear RNase P can be strongly inhibited by low concentrations of single-stranded RNAs and the yeast enzyme is relatively promiscuous in cleaving non-physiological RNA substrates (Chamberlain et al., 1996
), unlike the bacterial holoenzyme. This suggests that the nuclear holoenzyme has additional binding site(s) that might be used to position non-tRNA substrates for cleavage, although the in vitro
cleavage reactions do not faithfully reproduce specific recognition with purified enzyme and naked RNA. In turn, this suggests that nuclear RNase P must be prevented
from freely interacting with un-complexed, single-stranded RNA in the cell. Such a function for the protein complement would be compatible with the observations that RNases P and MRP are found in particular subcellular and subnuclear compartments—an arrangement that could serve the dual purpose of providing timely access to appropriate substrates and preventing access to inappropriate ones.
The RNase P ribozyme performs a relatively simple task, the hydrolysis of a phosphodiester bond, but the enzyme has evolved ever increasing ribonucleoprotein complexity to adapt to new cellular environments and tasks. Although we are beginning to understand the nature of the RNA in structure and catalysis, comprehension of these biological adaptations of the holoenzymes is at a very early stage.