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 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 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.

Circular RNA profiling reveals abundant and diverse circRNAs of SARS-CoV-2, SARS-CoV and MERS-CoV origin

2020 ◽  
Author(s):  
Shaomin Yang ◽  
Hong Zhou ◽  
Ruth Cruz-Cosme ◽  
Mingde Liu ◽  
Jiayu Xu ◽  
...  
Keyword(s):  
De Novo ◽  
Splice Junction ◽  
Circular Rna ◽  
Circular Rnas ◽  
Sequencing Data ◽  
Rna Profiling ◽  
Systematic Strategy ◽  
Coronavirus Infection ◽  
Abundance And Diversity ◽  
First Time

ABSTRACTCircular RNAs (circRNAs) encoded by DNA genomes have been identified across host and pathogen species as parts of the transcriptome. Accumulating evidences indicate that circRNAs play critical roles in autoimmune diseases and viral pathogenesis. Here we report that RNA viruses of the Betacoronavirus genus of Coronaviridae, SARS-CoV-2, SARS-CoV and MERS-CoV, encode a novel type of circRNAs. Through de novo circRNA analyses of publicly available coronavirus-infection related deep RNA-Sequencing data, we identified 351, 224 and 2,764 circRNAs derived from SARS-CoV-2, SARS-CoV and MERS-CoV, respectively, and characterized two major back-splice events shared by these viruses. Coronavirus-derived circRNAs are more abundant and longer compared to host genome-derived circRNAs. Using a systematic strategy to amplify and identify back-splice junction sequences, we experimentally identified over 100 viral circRNAs from SARS-CoV-2 infected Vero E6 cells. This collection of circRNAs provided the first line of evidence for the abundance and diversity of coronavirus-derived circRNAs and suggested possible mechanisms driving circRNA biogenesis from RNA genomes. Our findings highlight circRNAs as an important component of the coronavirus transcriptome.SummaryWe report for the first time that abundant and diverse circRNAs are generated by SARS-CoV-2, SARS-CoV and MERS-CoV and represent a novel type of circRNAs that differ from circRNAs encoded by DNA genomes.

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.

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.

scholarly journals UNDERSTANDING DISTAL TRANSCRIPTIONAL REGULATION FROM SEQUENCE, EXPRESSION AND INTERACTOME PERSPECTIVES

2010 ◽  
Vol 08 (02) ◽  
pp. 219-246 ◽  
Author(s):  
ARVIND RAO ◽  
DAVID J. STATES ◽  
ALFRED O. HERO ◽  
JAMES DOUGLAS ENGEL
Keyword(s):  
Computational Biology ◽  
De Novo ◽  
Sequence Data ◽  
Regulatory Elements ◽  
Proximal Promoter ◽  
Regulatory Sequences ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Specific Expression ◽  
Regulatory Regions

Gene regulation in eukaryotes involves a complex interplay between the proximal promoter and distal genomic elements (such as enhancers) which work in concert to drive precise spatio-temporal gene expression. The experimental localization and characterization of gene regulatory elements is a very complex and resource-intensive process. The computational identification of regulatory regions that confer spatiotemporally specific tissue-restricted expression of a gene is thus an important challenge for computational biology. One of the most popular strategies for enhancer localization from DNA sequence is the use of conservation-based prefiltering and more recently, the use of canonical (transcription factor motifs) or de novo tissue-specific sequence motifs. However, there is an ongoing effort in the computational biology community to further improve the fidelity of enhancer predictions from sequence data by integrating other, complementary genomic modalities. In this work, we propose a framework that complements existing methodologies for prospective enhancer identification. The methods in this work are derived from two key insights: (i) that chromatin modification signatures can discriminate proximal and distally located regulatory regions and (ii) the notion of promoter-enhancer cross-talk (as assayed in 3C/5C experiments) might have implications in the search for regulatory sequences that co-operate with the promoter to yield tissue-restricted, gene-specific expression.

scholarly journals In Vivo Addition of Poly(A) Tail and AU-Rich Sequences to the 3′ Terminus of the Sindbis Virus RNA Genome: a Novel 3′-End Repair Pathway

1999 ◽  
Vol 73 (3) ◽  
pp. 2410-2419 ◽  
Author(s):  
Ramaswamy Raju ◽  
Mustapha Hajjou ◽  
Kristie R. Hill ◽  
Vandana Botta ◽  
Sisir Botta
Keyword(s):  
Sindbis Virus ◽  
De Novo ◽  
Genome Replication ◽  
Sequence Motifs ◽  
Rna Sequences ◽  
Cytoplasmic Polyadenylation ◽  
Nontranslated Region ◽  
Rna Genome ◽  
Negative Sense

ABSTRACT Alphaviruses are mosquito-transmitted RNA viruses that cause important diseases in both humans and livestock. Sindbis virus (SIN), the type species of the alphavirus genus, carries a 11.7-kb positive-sense RNA genome which is capped at its 5′ end and polyadenylated at its 3′ end. The 3′ nontranslated region (3′NTR) of the SIN genome carries many AU-rich motifs, including a 19-nucleotide (nt) conserved element (3′CSE) and a poly(A) tail. This 3′CSE and the adjoining poly(A) tail are believed to regulate the synthesis of negative-sense RNA and genome replication in vivo. We have recently demonstrated that the SIN genome lacking the poly(A) tail was infectious and that de novo polyadenylation could occur in vivo (K. R. Hill, M. Hajjou, J. Hu, and R. Raju, J. Virol. 71:2693–2704, 1997). Here, we demonstrate that the 3′-terminal 29-nt region of the SIN genome carries a signal for possible cytoplasmic polyadenylation. To further investigate the polyadenylation signals within the 3′NTR, we generated a battery of mutant genomes with mutations in the 3′NTR and tested their ability to generate infectious virus and undergo 3′ polyadenylation in vivo. Engineered SIN genomes with terminal deletions within the 19-nt 3′CSE were infectious and regained their poly(A) tail. Also, a SIN genome carrying the poly(A) tail but lacking a part or the entire 19-nt 3′CSE was also infectious. Sequence analysis of viruses generated from these engineered SIN genomes demonstrated the addition of a variety of AU-rich sequence motifs just adjacent to the poly(A) tail. The addition of AU-rich motifs to the mutant SIN genomes appears to require the presence of a significant portion of the 3′NTR. These results indicate the ability of alphavirus RNAs to undergo 3′ repair and the existence of a pathway for the addition of AU-rich sequences and a poly(A) tail to their 3′ end in the infected host cell. Most importantly, these results indicate the ability of alphavirus replication machinery to use a multitude of AU-rich RNA sequences abutted by a poly(A) motif as promoters for negative-sense RNA synthesis and genome replication in vivo. The possible roles of cytoplasmic polyadenylation machinery, terminal transferase-like enzymes, and the viral polymerase in the terminal repair processes are discussed.

scholarly journals Closing the circle: current state and perspectives of circular RNA databases

2020 ◽  
Author(s):  
Marieke Vromman ◽  
Jo Vandesompele ◽  
Pieter-Jan Volders
Keyword(s):  
Splice Junction ◽  
Circular Rna ◽  
Circular Rnas ◽  
Working Mechanism ◽  
Comprehensive Overview ◽  
Specific Expression ◽  
Protein Coding ◽  
Rna Molecules ◽  
Current State ◽  
Coding Potential

Abstract Circular RNAs (circRNAs) are covalently closed RNA molecules that have been linked to various diseases, including cancer. However, a precise function and working mechanism are lacking for the larger majority. Following many different experimental and computational approaches to identify circRNAs, multiple circRNA databases were developed as well. Unfortunately, there are several major issues with the current circRNA databases, which substantially hamper progression in the field. First, as the overlap in content is limited, a true reference set of circRNAs is lacking. This results from the low abundance and highly specific expression of circRNAs, and varying sequencing methods, data-analysis pipelines, and circRNA detection tools. A second major issue is the use of ambiguous nomenclature. Thus, redundant or even conflicting names for circRNAs across different databases contribute to the reproducibility crisis. Third, circRNA databases, in essence, rely on the position of the circRNA back-splice junction, whereas alternative splicing could result in circRNAs with different length and sequence. To uniquely identify a circRNA molecule, the full circular sequence is required. Fourth, circRNA databases annotate circRNAs’ microRNA binding and protein-coding potential, but these annotations are generally based on presumed circRNA sequences. Finally, several databases are not regularly updated, contain incomplete data or suffer from connectivity issues. In this review, we present a comprehensive overview of the current circRNA databases and their content, features, and usability. In addition to discussing the current issues regarding circRNA databases, we come with important suggestions to streamline further research in this growing field.

Phenotypic Traits and Regulatory Role of RNA Folding in Molecular Selection

1991 ◽  
Vol 46 (7-8) ◽  
pp. 656-662
Author(s):  
Ariel Fernández
Keyword(s):  
Rna Folding ◽  
De Novo ◽  
Phenotypic Expression ◽  
Regulatory Role ◽  
Phenotypic Traits ◽  
Intermediate Structure ◽  
Rna Sequences ◽  
Rna Molecules ◽  
Molecular Selection

Abstract We concentrate on instances in which the phenotypic expression of information encoded in an RNA primary sequence might be revealed by the folding of the RNA itself. We have discov­ered that this situation finds concrete realization in the design of RNA molecules capable of maximizing the rate of autocatalytic synthesis when incubated with viral Qβ-replicase. This requires that we introduce the notion of phenotypic traits at the molecular level. Thus, the problem of finding RNA sequences whose phenotype favorably influences propagation amounts to finding RNA sequences which fold so as to optimize enzymatic performance and are in addition endowed with the proper recognition sites. The proof that these two problems are indeed equivalent has two steps: First we predict the metastable folded structures formed as a template RNA chain grows by sequential incorporation of nucleotides. The transient folded states appear to be involved in the regulation of the enzyme activity and they occur in a manner which is “oblivious” of thermodynamic time scales. Secondly, we compute the time-dependent activation energy for relaxation of each intermediate structure. This is done to establish constraints necessary for optimization of the regulatory role of RNA folding. The search for prospective template sequences is subject to such constraints. Our results aim at elucidating an optimization process realized by molecular selection in de novo (template-free) RNA synthesis by Qβ-replicase. We argue that the phenotype which mediates selection is given by metastable folding which emerges together with the printing of the genotype, that is, within the time span of a replication turnover.

scholarly journals Characterization of RNA content in individual phase-separated coacervate microdroplets

2021 ◽  
Author(s):  
Damian Wollny ◽  
Benjamin Vernot ◽  
Jie Wang ◽  
Maria Hondele ◽  
Anthony Hyman ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Rna World ◽  
Sequence Similarity ◽  
Central Component ◽  
Sequence Motifs ◽  
High Sequence Similarity ◽  
Specific Sequence ◽  
Rna Content ◽  
Wide Range

AbstractLiquid-liquid phase separation or condensation is a form of macromolecular compartmentalization. Condensates formed by complex coacervation were hypothesized to have played a crucial part during the origin-of-life. In living cells, condensation organizes biomolecules into a wide range of membraneless compartments. Although RNA is a key component of condensation in cells and the central component of the RNA world hypothesis, little is known about what determines RNA accumulation in condensates and how single condensates differ in their RNA composition. Therefore, we developed an approach to read the RNA content from single condensates using high-throughput sequencing. We find that RNAs which are enriched for specific sequence motifs efficiently accumulate in condensates. These motifs show high sequence similarity to short interspersed elements (SINEs). We observed similar results for protein-derived condensates, demonstrating applicability across different in vitro reconstituted membraneless organelles. Thus, our results provide a new inroad to explore the RNA content of phase-separated droplets at single condensate resolution.

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