Multiple structural flavors of RNase P in precursor tRNA processing

Abstract

The precursor transfer RNAs (pre‐tRNAs) require extensive processing to generate mature tRNAs possessing proper fold, structural stability, and functionality required to sustain cellular viability. The road to tRNA maturation follows an ordered process: 5′‐processing, 3′‐processing, modifications at specific sites, if any, and 3′‐CCA addition before aminoacylation and recruitment to the cellular protein synthesis machinery. Ribonuclease P (RNase P) is a universally conserved endonuclease in all domains of life, performing the hydrolysis of pre‐tRNA sequences at the 5′ end by the removal of phosphodiester linkages between nucleotides at position −1 and +1. Except for an archaeal species: Nanoarchaeum equitans where tRNAs are transcribed from leaderless‐position +1, RNase P is indispensable for life and displays fundamental variations in terms of enzyme subunit composition, mechanism of substrate recognition and active site architecture, utilizing in all cases a two metal ion‐mediated conserved catalytic reaction. While the canonical RNA‐based ribonucleoprotein RNase P has been well‐known to occur in bacteria, archaea, and eukaryotes, the occurrence of RNA‐free protein‐only RNase P in eukaryotes and RNA‐free homologs of Aquifex RNase P in prokaryotes has been discovered more recently. This review aims to provide a comprehensive overview of structural diversity displayed by various RNA‐based and RNA‐free RNase P holoenzymes towards harnessing critical RNA–protein and protein–protein interactions in achieving conserved pre‐tRNA processing functionality. Furthermore, alternate roles and functional interchangeability of RNase P are discussed in the context of its employability in several clinical and biotechnological applications.This article is categorized under: RNA Processing > tRNA Processing RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes