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

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 103
Author(s):  
Benjamin D. Lee ◽  
Eugene V. Koonin
Keyword(s):  
Plant Pathogens ◽  
Rna World ◽  
Unit Length ◽  
Circular Rna ◽  
Circular Rnas ◽  
Rolling Circle ◽  
Rna Molecules ◽  
Evolution Of Life ◽  
Rolling Circle Mechanism ◽  
Viral Nucleocapsid

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.

scholarly journals Parsimonious scenario for the emergence of viroid-like repliconsde novo

2019 ◽  
Author(s):  
Pablo Catalán ◽  
Santiago F. Elena ◽  
José A. Cuesta ◽  
Susanna Manrubia
Keyword(s):  
De Novo ◽  
Rna World ◽  
Circular Rna ◽  
Biochemical Properties ◽  
Circular Rnas ◽  
Sequence Motifs ◽  
Rna Sequences ◽  
Specific Sequence ◽  
Evolutionary Pathway ◽  
Rna Molecules

AbstractViroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or severalde novoindependent evolutionary origins in plants. Here we discuss the plausibility ofde novoemergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixed length, rod-like structures typical of Pospiviroidae are difficult to fix. Using different quantitative approaches, we evaluate the likelihood that RNA sequences fold into a rod-like structure and bear specific sequence motifs facilitating interactions with other molecules,e.g.RNA polymerases, RNases and ligases. By means of numerical simulations, we show that circular RNA replicons analogous to Pospiviroidae emerge if evolution is seeded with minimal circular RNAs that grow through the gradual addition of nucleotides. Further, these rod-like replicons often maintain their structure if independent functional modules are acquired that impose selective constraints. The evolutionary scenario we propose here is consistent with the structural and biochemical properties of viroids described to date.

scholarly journals Parsimonious Scenario for the Emergence of Viroid-Like Replicons De Novo

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 425 ◽  
Author(s):  
Pablo Catalán ◽  
Santiago F. Elena ◽  
José A. Cuesta ◽  
Susanna Manrubia
Keyword(s):  
De Novo ◽  
Rna World ◽  
Circular Rna ◽  
Biochemical Properties ◽  
Circular Rnas ◽  
Sequence Motifs ◽  
Rna Sequences ◽  
Specific Sequence ◽  
Evolutionary Pathway ◽  
Rna Molecules

Viroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or several de novo independent evolutionary origins in plants. Here, we discuss the plausibility of de novo emergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixed length, rod-like structures typical of Pospiviroidae are difficult to fix. Using different quantitative approaches, we evaluated the likelihood that RNA sequences fold into a rod-like structure and bear specific sequence motifs facilitating interactions with other molecules, e.g., RNA polymerases, RNases, and ligases. By means of numerical simulations, we show that circular RNA replicons analogous to Pospiviroidae emerge if evolution is seeded with minimal circular RNAs that grow through the gradual addition of nucleotides. Further, these rod-like replicons often maintain their structure if independent functional modules are acquired that impose selective constraints. The evolutionary scenario we propose here is consistent with the structural and biochemical properties of viroids described to date.

scholarly journals isoCirc catalogs full-length circular RNA isoforms in human transcriptomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruijiao Xin ◽  
Yan Gao ◽  
Yuan Gao ◽  
Robert Wang ◽  
Kathryn E. Kadash-Edmondson ◽  
...  
Keyword(s):  
Rolling Circle Amplification ◽  
Circular Rna ◽  
Human Cell Line ◽  
Full Length ◽  
Circular Rnas ◽  
Rna Seq ◽  
Short Read ◽  
Rolling Circle ◽  
Rna Molecules ◽  
Long Read

AbstractCircular RNAs (circRNAs) have emerged as an important class of functional RNA molecules. Short-read RNA sequencing (RNA-seq) is a widely used strategy to identify circRNAs. However, an inherent limitation of short-read RNA-seq is that it does not experimentally determine the full-length sequences and exact exonic compositions of circRNAs. Here, we report isoCirc, a strategy for sequencing full-length circRNA isoforms, using rolling circle amplification followed by nanopore long-read sequencing. We describe an integrated computational pipeline to reliably characterize full-length circRNA isoforms using isoCirc data. Using isoCirc, we generate a comprehensive catalog of 107,147 full-length circRNA isoforms across 12 human tissues and one human cell line (HEK293), including 40,628 isoforms ≥500 nt in length. We identify widespread alternative splicing events within the internal part of circRNAs, including 720 retained intron events corresponding to a class of exon-intron circRNAs (EIciRNAs). Collectively, isoCirc and the companion dataset provide a useful strategy and resource for studying circRNAs in human transcriptomes.

scholarly journals Natural 2′,5′-Phosphodiester Bonds Found at the Ligation Sites of Peach Latent Mosaic Viroid

2001 ◽  
Vol 75 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Fabien Côté ◽  
Dominique Lévesque ◽  
Jean-Pierre Perreault
Keyword(s):  
Circular Rna ◽  
Rolling Circle ◽  
Phosphodiester Bonds ◽  
Biological Importance ◽  
Rolling Circle Mechanism ◽  
Ligation Site

ABSTRACT Peach latent mosaic viroid (PLMVd) is a circular RNA pathogen that replicates in a DNA-independent fashion via a rolling circle mechanism. PLMVd has been shown to self-ligate in vitro primarily via the formation of 2′,5′-phosphodiester bonds; however, in vivo the occurrence and necessity of this nonenzymatic mechanism are not evident. Here, we unequivocally report the presence of 2′,5′-phosphodiester bonds at the ligation site of circular PLMVd strands isolated from infected peach leaves. These bonds serve to close the linear conformers (i.e., intermediates), yielding circular ones. Furthermore, these bonds are shown to stabilize the replicational circular templates, resulting in a significant advantage in terms of viroid viability. Although the mechanism responsible for the formation of these 2′,5′-phosphodiester bonds remains to be elucidated, a hypothesis describing in vivo nonenzymatic self-ligation is proposed. Most significantly, our results clearly show that 2′,5′-phosphodiester bonds are still present in nature and that they are of biological importance.

scholarly journals Viroids: unusual small pathogenic RNAs.

2004 ◽  
Vol 51 (3) ◽  
pp. 587-607 ◽  
Author(s):  
Anna Góra-Sochacka
Keyword(s):  
Secondary Structure ◽  
Hammerhead Ribozyme ◽  
Direct Interaction ◽  
Plant Diseases ◽  
Plant Host ◽  
Rolling Circle ◽  
Rna Molecules ◽  
Viroid Replication ◽  
Plant Genes ◽  
Rolling Circle Mechanism

Viroids are small (about 300 nucleotides), single-stranded, circular, non-encapsidated pathogenic RNA molecules. They do not code for proteins and thus depend on plant host enzymes for their replication and other functions. They induce plant diseases by direct interaction with host factors but the mechanism of pathogenicity is still unknown. They can alter the expression of selected plant genes important for growth and development. Viroids belong to two families, the Avsunviroidae and the Pospiviroidae. Viroids of the Avsunviroidae family adopt a branched or quasi rod-like secondary structure in their native state. Members of the Pospiviroidae family adopt a rod-like secondary structure. In such native structures five structural/functional domains have been identified: central (C), pathogenicity, variable and two terminal domains. The central conserved region (CCR) within the C domain characterizes viroids of the Pospiviroidae. Specific secondary structures of this region play an important role in viroid replication and processing. Viroids of the Avsunviroidae family lack a CCR but possess self-cleaving properties by forming hammerhead ribozyme structures; they accumulate and replicate in chloroplasts, whereas members of the Pospiviroidae family have a nuclear localization. Viroid replication occurs via a rolling circle mechanism using either a symmetric or asymmetric pathway in three steps, RNA transcription, processing and ligation.

Chemically synthesized circular RNAs with phosphoramidate linkages enable rolling circle translation

2020 ◽  
Vol 56 (46) ◽  
pp. 6217-6220
Author(s):  
Kosuke Nakamoto ◽  
Naoko Abe ◽  
Genichiro Tsuji ◽  
Yasuaki Kimura ◽  
Fumiaki Tomoike ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Stop Codon ◽  
Circular Rna ◽  
Circular Rnas ◽  
One Pot ◽  
Rolling Circle ◽  
Rna Fragments

Circular RNA without a stop codon enables rolling circle translation. we carried out one-pot chemical synthesis of circular RNA from RNA fragments. The synthesized circular RNAs acted as translation templates, despite the presence of unnatural phosphoramidate linkages.

scholarly journals N6-Methyladenosine Modification Opens a New Chapter in Circular RNA Biology

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Wu ◽  
Xin Guo ◽  
Yi Wen ◽  
Shangqing Huang ◽  
Xiaohui Yuan ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Circular Rna ◽  
Regulatory Mechanisms ◽  
Circular Rnas ◽  
Biological Functions ◽  
Future Directions ◽  
Rna Molecules ◽  
Physiological Processes ◽  
Rna Biology ◽  
Insight Into

As the most abundant internal modification in eukaryotic cells, N6-methyladenosine (m6A) in mRNA has shown widespread regulatory roles in a variety of physiological processes and disease progressions. Circular RNAs (circRNAs) are a class of covalently closed circular RNA molecules and play an essential role in the pathogenesis of various diseases. Recently, accumulating evidence has shown that m6A modification is widely existed in circRNAs and found its key biological functions in regulating circRNA metabolism, including biogenesis, translation, degradation and cellular localization. Through regulating circRNAs, studies have shown the important roles of m6A modification in circRNAs during immunity and multiple diseases, which represents a new layer of control in physiological processes and disease progressions. In this review, we focused on the roles played by m6A in circRNA metabolism, summarized the regulatory mechanisms of m6A-modified circRNAs in immunity and diseases, and discussed the current challenges to study m6A modification in circRNAs and the possible future directions, providing a comprehensive insight into understanding m6A modification of circRNAs in RNA epigenetics.

scholarly journals ICTV Virus Taxonomy Profile: Pospiviroidae

2020 ◽  
Author(s):  
Francesco Di Serio ◽  
Robert A. Owens ◽  
Shi-Fang Li ◽  
Jaroslav Matoušek ◽  
Vicente Pallás ◽  
...  
Keyword(s):  
Circular Rna ◽  
Virus Taxonomy ◽  
Hammerhead Ribozymes ◽  
Rolling Circle ◽  
Link Type ◽  
The Family ◽  
Rolling Circle Mechanism ◽  
Conserved Region

Members of the family Pospiviroidae have single-stranded circular RNA genomes that adopt a rod-like or a quasi-rod-like conformation. These genomes contain a central conserved region that is involved in replication in the nucleus through an asymmetric RNA–RNA rolling-circle mechanism. Members of the family Pospiviroidae lack the hammerhead ribozymes that are typical of viroids classified in the family Avsunviroidae. The family Pospiviroidae includes the genera Apscaviroid, Cocadviroid, Coleviroid, Hostuviroid and Pospiviroid, with >25 species. This is a summary of the ICTV Report on the family Pospiviroidae, which is available at ictv.global/report/pospiviroidae.

Modeling prebiotic catalysis with nucleic acid-like polymers and its implications for the proposed RNA world

2004 ◽  
Vol 76 (12) ◽  
pp. 2085-2099 ◽  
Author(s):  
S. G. Srivatsan
Keyword(s):  
Nucleic Acid ◽  
De Novo ◽  
Rna World ◽  
Acid Synthesis ◽  
Polymerization Process ◽  
Rna Molecules ◽  
Catalytic Material ◽  
Evolution Of Life ◽  
Prebiotic Catalysis

The theory that RNA molecules played a pivotal role in the early evolution of life is now widely accepted. Studies related to this hypothetical “RNA world” include three major areas: the formation of precursors for the first RNA molecules, the polymerization process, and the potential of RNA to catalyze chemical and biochemical reactions. Several chemical and biochemical studies performed under simulated prebiotic conditions support the role of RNA as both genetic as well as catalytic material. However, owing to the lack of credible mechanism for de novo nucleic acid synthesis and the hydrolytic instability of RNA molecules, there has been some serious discussion of whether biopolymers that closely resembled nucleic acid preceded the “RNA world”. In this context, an overview of prebiotic chemistry, the role of mineral surface, and the significance of studies related to RNA-like polymers in the origin of life are presented here.

Viroids with Hammerhead Ribozymes: Some Unique Structural and Functional Aspects with Respect to Other Members of the Group

1999 ◽  
Vol 380 (7-8) ◽  
pp. 849-854 ◽  
Author(s):  
R. Flores ◽  
J.-A. Navarro ◽  
M. de la Peña ◽  
B. Navarro ◽  
S. Ambrós ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Rna Polymerase ◽  
Circular Rna ◽  
Hammerhead Ribozymes ◽  
Rolling Circle ◽  
Rna Ligase ◽  
Functional Aspects ◽  
Chlorotic Mottle ◽  
Pathogenicity Determinant ◽  
Rolling Circle Mechanism

AbstractViroids, subviral pathogens of plants, are composed of a single-stranded circular RNA of 246–399 nucleotides. Within the 27 viroids sequenced, avocado sunblotch, peach latent mosaic and chrysanthemum chlorotic mottle viroids (ASBVd, PLMVd and CChMVd, respectively) can form hammerhead structures in both of their polarity strands. These ribozymes mediate self-cleavage of the oligomeric RNAs generated in the replication through a rolling circle mechanism, whose two other steps are catalyzed by an RNA polymerase and an RNA ligase. ASBVd, and presumably PLMVd and CChMVd, replicate and accumulate in the chloroplast, whereas typical viroids replicate and accumulate in the nucleus. PLMVd and CChMVd do not adopt a rod-like or quasi rod-like secondary structure as typical viroids do but have a highly branched conformation. A pathogenicity determinant has been mapped in a defined region of the CChMVd molecule.

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