© 2004 Robert A. Freitas Jr. and Ralph C. Merkle. All Rights Reserved.

Robert A. Freitas Jr., Ralph C. Merkle, Kinematic Self-Replicating Machines, Landes Bioscience, Georgetown, TX, 2004.

4.3.2 Viroids

Subviral plant pathogens first discovered in 1971 [1741], viroids and viroid-like RNAs [1742] are small, single-stranded, closed-circuit RNA molecules existing as highly base-paired rod-like structures (Figure 4.13) without protein coats (i.e., without capsids). Viroids typically contain 246-401 nucleotides [1743], have mass ~100 kD, have a compact secondary structure, lack mRNA activity [1744], and replicate autonomously (Figure 4.14) when inoculated into their host plants [1743].

Viroids replicate themselves only in an intracellular environment. Notes Flores [1743] in a recent review: “In contrast to viruses, viroids do not code for any protein and depend on host enzymes [e.g., a specific RNA-dependent RNA polymerase] for their replication, which in some viroids occurs in the nucleus [usually in nucleoli] and in others [occurs] in the chloroplast, through a rolling-circle mechanism with three catalytic steps. Quite remarkably, however, one of the steps, cleavage of the oligomeric head-to-tail replicative intermediates to unit-length strands, is mediated in certain viroids by hammerhead ribozymes that can be formed by their strands of both polarities. Viroids induce disease by direct interaction with host factors, the nature of which is presently unknown. Some properties of viroids, particularly the presence of ribozymes, suggest that they might have appeared very early in evolution and could represent ‘living fossils’ of the precellular RNA world that presumably preceded our current world based on DNA and proteins.” Along with human hepatitis delta virus (vHDV), viroids are the smallest known natural auto-replicable RNAs [1742] or “autonomous replicons” [1747, 1748]. (Spiegelman’s mutant molecule (Section 5.5) is a slightly smaller RNA strand but requires a very specialized unnatural environment in which to replicate.)

Viroid replication rate following the symmetric pathway can be crudely estimated by applying the 50-100 nucleotide/sec rate constant typical of bacterial RNA polymerases to the 246-401 viroid bases, then adding two hammerhead- or RNAase-mediated cleavages of intermediates which occur at a 1.5 min^-1 rate (~40 sec per cleavage) [1749], gives an estimated ideal viroid replication time of ~ 80-90 sec.

Computer simulations of viroid folding pathways [1750] are the first step towards the rational design of artificial viroids.

Last updated on 1 August 2005