Viroids: self-replicating, mobile, and fast-evolving noncoding regulatory RNAs.

Viroids are small, circular, and noncoding RNAs that infect plants. They replicate in the nucleus or chloroplast and then traffic from cell to cell and from organ to organ to establish systemic infection. Viroids achieve nearly all of the biological functions by directly interacting with host cellular factors. Viroid replication, together with replication of human hepatitis delta virus, demonstrates the biological novelty and significance of RNA-dependent RNA polymerase activities of DNA-dependent RNA polymerases. Viroid systemic infection uncovers a new biological principle--the role of three-dimensional RNA structural motifs mediating RNA trafficking between specific cells. Viroid diseases are virtually the consequences of host gene regulation by noncoding RNAs. A viroid RNA has the highest in vivo mutation rate among all known nucleic acid replicons. The host range of many viroids is expanding, essentially as a result of continuing and fast evolution of noncoding sequences/structures to gain new biological functions. Here, I discuss recent progress in these areas, emphasizing the broad significance of viroid research to the discovery of fundamental biological principles.