The Dynamic Network of RNP RNase P Subunits.

Athanasios-Nasir Shaukat,Eleni G Kaliatsi,Constantinos Stathopoulos,Ilias Skeparnias

doi:10.3390/ijms221910307

Athanasios-Nasir Shaukat, Eleni G Kaliatsi + Show 2 more

Open Access

https://doi.org/10.3390/ijms221910307

Copy DOI

Abstract

Ribonuclease P (RNase P) is an important ribonucleoprotein (RNP), responsible for the maturation of the 5′ end of precursor tRNAs (pre-tRNAs). In all organisms, the cleavage activity of a single phosphodiester bond adjacent to the first nucleotide of the acceptor stem is indispensable for cell viability and lies within an essential catalytic RNA subunit. Although RNase P is a ribozyme, its kinetic efficiency in vivo, as well as its structural variability and complexity throughout evolution, requires the presence of one protein subunit in bacteria to several protein partners in archaea and eukaryotes. Moreover, the existence of protein-only RNase P (PRORP) enzymes in several organisms and organelles suggests a more complex evolutionary timeline than previously thought. Recent detailed structures of bacterial, archaeal, human and mitochondrial RNase P complexes suggest that, although apparently dissimilar enzymes, they all recognize pre-tRNAs through conserved interactions. Interestingly, individual protein subunits of the human nuclear and mitochondrial holoenzymes have additional functions and contribute to a dynamic network of elaborate interactions and cellular processes. Herein, we summarize the role of each RNase P subunit with a focus on the human nuclear RNP and its putative role in flawless gene expression in light of recent structural studies.

Highlights

Ribonuclease P (RNase P) is an important ribonucleoprotein (RNP), responsible for the maturation of the 5 end of precursor tRNAs
Ribonuclease P (RNase P) is an essential endoribonuclease that was first characterized by Sidney Altman almost 40 years ago in E. coli, as a complex of one protein subunit (RnpA or C5 protein; 119 aa; 13,789 Da) and an RNA subunit (M1 RNA; 377 nt)
The bacterial RNase P holoenzyme consists of a single RNA subunit and one rather small protein, studies on RNase P from several archaea showed a more complex ribonucleoprotein, of one RNase P RNA is a Type-A subunit (P RNA) (RPR) and five protein subunits

Summary

The Discovery of Different RNase P Facets

Ribonuclease P (RNase P) is an essential endoribonuclease that was first characterized by Sidney Altman almost 40 years ago in E. coli, as a complex of one protein subunit (RnpA or C5 protein; 119 aa; 13,789 Da) and an RNA subunit (M1 RNA; 377 nt). Several previous studies on the reconstitution of the archaeal and eukaryotic enzymes provided an outline of the RNA–protein and protein–protein interactions, the structure of the human nuclear RNase P, both in its apo form and in complex form with tRNAVal, provided the detailed architecture of the RNP and highlighted the importance of protein subunits in the assembly and the function of the holoenzyme. Two distinct subunits of Rpp were found in the human RNase P holoenzyme, in close contact to Pop, Rpp and Rpp (forming the “palm” module), as well as domains of the RPPH1 essential for catalysis, suggesting that the loss of Rpp may introduce substantial instability to the RNP (Figure 1) [5]. The role of the Rpp20–Rpp25–Pop1–Pop subcomplex in the production of RPR is essential and highlights the importance of protein subunit interactions for the assembly of the RNase P holoenzyme, which is coupled to RPR transcription [93]

Rpp21–Rpp29 and Their Role in RNase P Activity and Beyond

Human Mitochondrial RNase P