Viroids and Viroid-like Circular RNAs: Do They Descend from Primordial Replicators?

Abstract

Viroids are a unique class of plant pathogens that consist of small circular RNA molecules, between 220 and 450 nucleotides in size. Viroids encode no proteins and are the smallest known infectious agents. Viroids replicate via the rolling circle mechanism, producing multimeric intermediates which are cleaved to unit length either by ribozymes formed from both polarities of the viroid genomic RNA or by coopted host RNAses. Many viroid-like small circular RNAs are satellites of plant RNA viruses. Ribozyviruses, represented by human hepatitis delta virus, are larger viroid-like circular RNAs that additionally encode the viral nucleocapsid protein. It has been proposed that viroids are direct descendants of primordial RNA replicons that were present in the hypothetical RNA world. We argue, however, that much later origin of viroids, possibly, from recently discovered mobile genetic elements known as retrozymes, is a far more parsimonious evolutionary scenario. Nevertheless, viroids and viroid-like circular RNAs are minimal replicators that are likely to be close to the theoretical lower limit of replicator size and arguably comprise the paradigm for replicator emergence. Thus, although viroid-like replicators are unlikely to be direct descendants of primordial RNA replicators, the study of the diversity and evolution of these ultimate genetic parasites can yield insights into the earliest stages of the evolution of life.

Self-empowerment of life through RNA networks, cells and viruses

“…The self-ligation of different parts of RNA stem-loop groups occurs at single-stranded RNA parts ( Gwiazda et al ., 2012 ). Here, it is important to note that circular RNAs are protected against endonuclease degradations and therefore represent an evolutionary benefit in this early stage of the RNA world ( Lasda & Parker, 2014 ; Müller, 2015 ; Lee & Koonin, 2022 ; Rivera-Madrinan, Di Iorio, & Higgs, 2022 ). With the emergence of the RNA polymerase ribozyme, functional RNA molecules, including the polymerase itself, could be copied ( Attwater, Wochner, & Holliger, 2013 ; Tjhung, Shokhirev, Horning, & Joyce, 2020 ).…”

A compositional view comparing modern biological condensates and primitive phase‐separated compartments

“…These viroids are small, circular RNA molecules that infect plants and replicate autonomously, not using their own proteins but rather the proteins of the host for replication. [133,134] Similarly, the discovery of self-replicating RNA molecules, or replicators, that can evolve in the absence of proteins further lends to the possibility that RNA-based replicators could have given rise to the first viruses. [135] In fact, virus-like RNA has been postulated to have facilitated the transfer of genetic material between RNA, helping to select for more efficient replicators, contributing to the continued evolution of organisms, and culminating in the DNA world!…”

Design principles and applications of synthetic self‐replicating RNAs

“…The replication of viroids and ribozyviruses has been reviewed in great detail by Flores et al (2011) and Lee and Koonin (2022). Generally, replication of circular RNAs of ribozyviruses, viroids, and potentially ambiviruses is based on rolling‐circle replication (Flores et al, 2011).…”