Unexpected diversity of RNase P, an ancient tRNA processing enzyme: challenges and prospects

Abstract

For an enzyme functioning predominantly in a seemingly housekeeping role of 5' tRNA maturation, RNase P displays a remarkable diversity in subunit make-up across the three domains of life. Despite the protein complexity of this ribonucleoprotein enzyme increasing dramatically from bacteria to eukarya, the catalytic function rests with the RNA subunit during evolution. However, the recent demonstration of a protein-only human mitochondrial RNase P has added further intrigue to the compositional variability of this enzyme. In this review, we discuss some possible reasons underlying the structural diversity of the active sites, and use them as thematic bases for elaborating new directions to understand how functional variations might have contributed to the complex evolution of RNase P.

Figure 1

A cladogram depicting a possible scheme for evolution of RNA-based RNase P (see sections 1 and 4 for details). Scales are arbitrary. LUCA, last universal common ancestor; RPR, RNase P RNA; RPP, RNase P protein.

Figure 2

Substrate recognition and catalysis by bacterial RNase P (see section 3 for details). (A) Secondary structures of the E. coli RPR (left) and a pre-tRNA (right) illustrating the domains required for interactions during RNase P catalysis. The interaction of the leader sequence in the pre-tRNA (bold, dashed line) with the RPP is also indicated. TBS, T stem-loop-binding site. (B) A close-up view showing one model of the canonical RNase P cleavage site. Chemical groups (black spheres) and Mg²⁺ (red spheres) suggested to contribute to catalysis are marked. Also depicted is a Mg²⁺-activated hydroxide nucleophile (arrow), which attacks the phosphorous atom in the scissile bond.