Replication and Evolution of Viroid-Like Pathogens

Abstract

It is becoming increasingly evident that certain basic processes of macromolecular biology require RNA. Whether as a key component of ribosomes in the translation process, or as small nuclear RNAs in particles carrying out eukaryotic messenger RNA (mRNA) splicing, RNA—perhaps because of its historical role in molecular evolution—occupies a central position. Another class of RNA molecules—the pathogenic viroid-like RNAs—are also providing new insights into the role of RNA in gene expression. Until recently, these circular, self-replicating RNAs—250–400 bases in length—were found only in plants. Beginning in 1986, however, several reports have confirmed that the causative agent for delta hepatitis in mammals contains a circular, viroid-like RNA (Wang et al. 1986; Kos et al.1986; Chen et al. 1986; Taylor et al. 1987). This delta RNA is about four times the size of plant viroid RNAs. Knowledge that such RNAs can proliferate within cells has come at the same time as an increasing interest in the role of RNA in the evolution of primitive self-replicating systems. Several proposals based on RNA—a material with both template and enzymatic properties—as the initial genetic substance have appeared (Gilbert 1986; Sharp 1985).