Molecule of the Month: Ribonuclease P

Most of the chemical reactions performed inside cells are catalyzed by enzymes. However, in some specialized cases, RNA is used to build a catalytic active site to form a ribozyme. For example, self-splicing RNA cuts itself out of a longer RNA strand without any need for help by a protein. Ribonuclease P (RNase P), RNase MRP, and ribosomes are examples of ribozymes that perform key roles in the biosynthesis of proteins. RNase P cleaves pre-tRNA, generating tRNA (transfer RNA) molecules with mature 5’ ends. RNase MRP makes cuts in the RNA inside ribosomes as they are constructed, and ribosomes build new proteins using a reaction that is catalyzed by the ribosomal RNA.

Transfer RNA facilitates protein synthesis by matching three-nucleotide codons of nucleic acids to their corresponding amino acids. As this process is paramount for cell survival, tRNA molecules are highly regulated and undergo extensive structural modifications after they are transcribed as pre-tRNA. Shown here in PDB entry 6ahu, the endonuclease RNase P cuts a small precursor segment from the 5' end of pre-tRNA, producing a mature tRNA molecule ready to do its job. Human nuclear RNase P is comprised of 10 proteins and a large catalytic RNA strand. The individual protein components serve to stabilize and orient the RNA is such a way that allows for tRNA recognition and subsequent catalysis.

While both bacteria and archaea have just one type of RNase P, some eukaryotes have two kinds of pre-tRNA cleavers: a ribozyme RNase P that contains a catalytic RNA strand and a form that lacks RNA altogether, called protein-only RNase P (PRORP). Although both endonucleases perform the same function, they differ in both cellular location and structure. PRORP works in the mitochondria, cutting pre-tRNA involved in the expression of genes crucial for energy production that are encoded by a separate mitochondrial genome. The RNA-based RNase P, on the other hand, modifies pre-tRNA in the nucleus. Protein subunits of PRORP and RNA-based RNase P have analogous function but share no structural homology.

RNase P is one of two ribozymes present in nearly all organisms, the other being the ribosome. Remarkably, the RNA is very similar in bacterial, archaeal, and eukaryotic nuclear RNase P. This is evidence that a form of RNase P was present before the diversification of the three kingdoms of life and that it may have evolved in an ancient RNA-based world. The major differences are seen in the protein content: more complex organisms generally contain a greater number of protein subunits. As shown in PDB entry 3q1q (top left), bacterial RNase P has a small protein subunit that accounts for only 10% of the total mass. Also shown is PDB entry 6k0b (top right), an archaeal RNase P that functions as a dimer with eight protein subunits, and PDB entry 6ahu (bottom), a human nuclear RNase P with ten protein subunits.