Uncovered diversity of infectious circular RNAs: A new paradigm for the minimal parasites?

Infectious circular RNAs (circRNAs) have been considered as biological oddities only occurring in plants, with limited exceptions. However, a great diversity of viroid-like circRNAs has been recently uncovered by the high-throughput exploration of transcriptomic data of geographically and ecologically diverse niches. In my opinion, this suggests a change in basic assumptions regarding our knowledge about these minimal parasites. The potentially infectious circRNAs found are diverse in size, type of ribozymes, encoded proteins and potential host organisms. The distinction between viroids and RNA viruses has been blurred by the detection of circular mitoviruses and ambiviruses which encode for their own RNA-dependent RNA polymerase. Thus, their taxonomic classification might pose a challenge because of the apparent extensive horizontal transfer and recombination of sequences. Many aspects of the predicted circRNAs remain to be uncovered, such as their pathogenicity or host range, and experimental validations are essential. For example, viroid-like circRNAs similar in size to plant viroids have been found to replicate and cause symptoms in fungi, with an isolate being the smallest replicon characterized so far. Despite an ancestral prebiotic origin for viroid-like sequences has been proposed, their dependence of viral or cellular proteins seems, to my view, more compatible with a cellular escape and/or viral genome reduction. This wide variety of potentially infectious agents might pose a biohazard concern of which we were previously unaware, and thus it would be convenient that more efforts are assigned for their characterization.