Piece by piece: Building a ribozyme

Abstract

The ribosome and RNase P are cellular ribonucleoprotein complexes that perform peptide bond synthesis and phosphodiester bond cleavage, respectively. Both are ancient biological assemblies that were already present in the last universal common ancestor of all life. The large subunit rRNA in the ribosome and the RNA subunit of RNase P are the ribozyme components required for catalysis. Here, we explore the idea that these two large ribozymes may have begun their evolutionary odyssey as an assemblage of RNA "fragments" smaller than the contemporary full-length versions and that they transitioned through distinct stages along a pathway that may also be relevant for the evolution of other non-coding RNAs.

Keywords: enzyme catalysis; evolution; ribonuclease P (RNase P); ribonucleoprotein complex; ribosome; ribozyme (catalytic RNA) (RNA enzyme).

Figure 1.

Model for the stepwise conversion of split rRNA genes into a contiguous, single unit. RNA species 4 is depicted as containing a primitive, self-folding PTC domain to emphasize that peptide bond formation would have been supported at the earliest stages of this evolutionary pathway. MacPyMOL was used to generate the LSU rRNA structure in the center (Protein Data Bank code 1FFK; Haloarcula marismortui). Adapted from Refs. and . This research was originally published in Tracing Biological Evolution in Protein and Gene Structures (Gō, M., and Schimmel, P., eds). Gray, M. W., Greenwood, S. J., Smallman, D. S., Spencer, D. F., and Schnare, M. N. Ribosomal RNA in pieces: a modern paradigm of the primordial ribosome. 1995; 65–76. © Elsevier Science B.V. and in Ribosomal RNA: Structure, Evolution, Processing, and Function in Protein Biosynthesis (Zimmermann, R. A., and Dahlberg, A. E., eds). Gray, M. W., and Schnare, M. N. Evolution of rRNA gene organization. 1996; 49–69. © CRC Press, Inc.

Figure 2.

Gene content and arrangement in the linear mitochondrial genome of the chlorophyte alga, C. reinhardtii (39, 56), showing the scrambled arrangement of subgenic SSU (S) and LSU (L) rRNA-coding modules, which are interspersed and co-transcribed with protein-coding and tRNA genes (W, Q, M). Protein-coding genes specify subunits of electron transport chain Complex I (nad1, nad2, nad4, nad5, and nad6), Complex III (cob), and Complex IV (cox1), as well as a reverse transcriptase-like protein (rtl). Arrows, putative promoters. SSU rRNA– and LSU rRNA–coding modules are numbered in the 5′-to-3′ transcriptional order of the corresponding sequences in their covalently continuous rRNA counterparts. Adapted from Ref. . This research was originally published in Current Genetics. Boer, P. H., and Gray, M. W. Transfer RNA genes and the genetic code in Chlamydomonas reinhardtii mitochondria. Curr. Genet. 1988; 14:583–590. © Springer.

Figure 3.

Gradual conversion of the RPR from a cis-cleaving to a trans-acting ribozyme capable of processing multiple RNA substrates. MacPyMOL was used to generate the RPR depictions (Protein Data Bank code 3Q1R, 28). Adapted in part from (32).

Figure 4.

Schematic depicting thematic parallels in substrate recognition by aminoacyl-tRNA synthetases and RNase P (see “RNase P” for details). MacPymol was used to generate the RPR and tRNA depictions (Protein Data Bank Code 3Q1R, 28).