The ubiquitous occurrence of ribonuclease P (RNase P) as a ribonucleop
rotein and the catalytic properties of bacterial RNase P RNAs indicate
that RNA fulfills an ancient and important role in the function of th
is enzyme. This review focuses on efforts to determine the structure o
f the bacterial RNase P RNA ribozyme. Phylogenetic comparative analysi
s of a library of bacterial RNase P RNA sequences has resulted in a we
ll-developed secondary structure model and allowed identification of s
ome elements of tertiary structure. The native structure has been rede
signed by circular permutation to facilitate intra- and inter-molecula
r crosslinking experiments in order to gain further structural informa
tion. The crosslinking constraints, together with the constraints prov
ided by comparative analyses, have been incorporated into a first-orde
r model of the structure of the ribozyme-substrate complex. The develo
ping structural perspective allows the design of self-cleaving pre-tRN
A-RNase P RNA conjugates which are useful tools for additional structu
re-probing experiments.