RNA virus evolution and the control of viral disease

RNA molecules display several features — some of which have been recognized only very recently — that contribute to their potential for modification and evolution. Cellular transcripts as well as autonomous RNA genetic elements may possess catalytic activity [1–3]. The following examples demonstrate the catalytic ability of RNA molecules, an activity which in the past was associated only with proteins. The active site of ribonuclease P — an enzyme that processes precursor tRNA molecules — resides in RNA [4,5]. Excision of the intervening sequence and subsequent splicing of Tetrahymena rRNA [6,7] is a protein-independent process. Regarding autonomous genetic elements, replication of viroids and certain plant virus satellites involves some protein-free RNA modification steps [8–12]. The catalytic potential of RNA includes hydrolysis of substrate RNA molecules in trans [13,14] and addition of nucleotides to preexisting chains [15–17]. Thus, biological catalysis, embodied in polynucleotide chains, adds to the potential for generating novel molecules in evolving RNA populations. This has strengthened the belief in a central role of RNA or of RNA-like molecules in the self-organization of a genetic memory and the early evolution of life on earth [18–20].