RNase P

Ribonuclease P (RNase P) is a type of Ribonuclease and is currently under heavy research. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein based enzyme would. Its function is to cleave off an extra, or precursor, sequence of RNA on tRNA molecules ^[1]. Further RNase P is one of two known multiple turnover ribozymes in nature (the other being the ribosome), the discovery of which earned Professor Sidney Altman the Nobel Prize in Chemistry in 1989. In fact, Sidney Altman discovered the existence of precursor tRNA with flanking sequences and was the first to characterize RNase P and its activity in processing of the 5' leader sequence of precursor tRNA back in the 70's. Recent findings also reveal that RNase P has a new function ^[2]. It has been shown that human nuclear RNase P is required for the normal and efficient transcription of various small noncoding RNA genes, such as tRNA, 5S rRNA, SRP RNA and U6 snRNA genes ^[3], which are transcribed by RNA polymerase III, one of three major nuclear RNA polymerases in human cells.

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In bacteria

Further information: Bacterial RNase P class A and Bacterial RNase P class B

In bacteria, such as E. coli, RNase P has two components: an RNA chain, called M1 RNA, and a polypeptide chain, or protein, called C5 protein ^[4], ^[5]. In vivo, both components are necessary for the ribozyme to function properly, but in vitro, the M1 RNA can act alone as a catalyst ^[1]. The primary role of the C5 protein is to enhance the substrate binding affinity and the catalytic rate of the M1 RNA enzyme probably by increasing the metal ion affinity in the active site. The crystal structure of bacterial RNase P RNA has been recently resolved, revealing its flat surface that is generated by a number of coaxially stacked helical domains connected by local and long-range contacts. This flat surface facilitates binding and cleavage of precursor tRNA substrates. For review see ^[4].

In archaea

Further information: Archaeal RNase P

In archaea, RNase P ribonucleoproteins consist of 4-5 protein subunits that are associated with RNA. As revealed by in vitro reconstitution experiments these protein subunits are individually dispensable for tRNA processing that is essentially mediated by the RNA component ^[6], ^[7], ^[8]. The structures of protein subunits of archaeal RNase P have been resolved by x-ray crystallography and NMR, thus revealing new protein domains and folding fundamental for function.

In eukaryotes

Further information: Nuclear RNase P

In eukaryotes, such as humans and yeast, RNase P consists of an RNA chain that is structurally similar to that found in bacteria ^[9] as well as nine to ten associated proteins (as opposed to the single bacterial RNase P protein, C5) ^[2], ^[10] . Five of these protein subunits exhibit homology to archaeal counterparts. These protein subunits of RNase P are shared with RNase MRP ^[10], ^[11], ^[12], a catalytic ribonucleoprotein involved in processing of ribosomal RNA in the nucleolus ^[13]. RNase P RNA from eukaryotes was only recently demonstrated to be a ribozyme ^[14]. Accordingly, the numerous protein subunits of eucaryal RNase P have a minor contribution to tRNA processing per se ^[15], while they seem to be essential for the function of RNase P and RNase MRP in other biological settings, such as gene transcription and the cell cycle ^[3], ^[16].

References

• MeSH RNase+P
• EC 3.1.26.5