Archaeal/eukaryal RNase P: subunits, functions and RNA diversification

Abstract

RNase P, a catalytic ribonucleoprotein (RNP), is best known for its role in precursor tRNA processing. Recent discoveries have revealed that eukaryal RNase P is also required for transcription and processing of select non-coding RNAs, thus enmeshing RNase P in an intricate network of machineries required for gene expression. Moreover, the RNase P RNA seems to have been subject to gene duplication, selection and divergence to generate two new catalytic RNPs, RNase MRP and MRP-TERT, which perform novel functions encompassing cell cycle control and stem cell biology. We present new evidence and perspectives on the functional diversification of the RNase P RNA to highlight it as a paradigm for the evolutionary plasticity that underlies the extant broad repertoire of catalytic and unexpected regulatory roles played by RNA-driven RNPs.

Figure 1.

Conservation and evolution of the RNA and protein subunits of RNase P. Archaeal RNase P has five proteins: Rpp21, Rpp29, Rpp30, Pop5 and Rpp38 (L7Ae). The association of Alba with archaeal RNase P remains in question (see text). Human nuclear RNase P has ten distinct protein subunits, termed Rpp14, Rpp20, Rpp21, Rpp25, Rpp29, Rpp30, Rpp38, Rpp40, Pop1 and Pop5. Five of these subunits share archaeal homologs. Rpp20 and Rpp25 are homologous to Alba in archaea. In Eukarya, an ancestral RNase P RNA likely gave rise to RNase MRP RNA by a gene duplication mechanism; MRP RNA is part of RNase MRP and MRP-TERT (see text). Except for Rpp21, all the other proteins of human RNase P are shared by RNase MRP, but it remains unknown if these proteins are also associated with MRP-TERT. In S. cerevisiae, nucleolar RNase MRP possesses two additional proteins, termed RMP1 and SNM1 (see ref. 111 and references therein); it is unknown if these two specific subunits have homologs in human RNase MRP. The protein shapes are not drawn to scale.

Figure 2.

A model for association of human RNase P with Pol III and tRNA genes. Schematic of a tRNA gene with conserved internal boxes A and B regulatory elements bound by the transcription factors TFIIIC and TFIIIB. These two transcription factors recruit Pol III. Human nuclear RNase P associates with Pol III and with the tRNA gene (69). This may facilitate coordination of transcription and tRNA processing, and involve other tRNA processing and modifying activities (indicated by question marks).

Figure 3.

An RNase P RNA-like gene exists in the human genome. (A) Profile generated by the UCSC Genome Browser software showing the conservation from primates to fish (stickleback) of the human RPPH gene (located in chromosome 14). Human chained self-alignment reveals the existence of an RNase P RNA-like gene in chromosome 4 (last stripe). (B) In contrast to the RPPH gene, the RNase P RNA-like gene could be computationally detected only in Rhesus.