In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for (...) the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users. (shrink)

Identification of non-coding RNAs (ncRNAs) has been significantly improved over the past decade. On the other hand, semantic annotation of ncRNA data is facing critical challenges due to the lack of a comprehensive ontology to serve as common data elements and data exchange standards in the field. We developed the Non-Coding RNA Ontology (NCRO) to handle this situation. By providing a formally defined ncRNA controlled vocabulary, the NCRO aims to fill a specific and highly needed niche in semantic (...) annotation of large amounts of ncRNA biological and clinical data. (shrink)

Identification of non-coding RNAs (ncRNAs) has been significantly enhanced due to the rapid advancement in sequencing technologies. On the other hand, semantic annotation of ncRNA data lag behind their identification, and there is a great need to effectively integrate discovery from relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a precisely defined ncRNA controlled vocabulary, which can fill a specific and highly needed niche in unification of ncRNA biology.

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for (...) the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. (shrink)

The Plant Ontology (PO; http://www.plantontology.org/) is a publicly-available, collaborative effort to develop and maintain a controlled, structured vocabulary (“ontology”) of terms to describe plant anatomy, morphology and the stages of plant development. The goals of the PO are to link (annotate) gene expression and phenotype data to plant structures and stages of plant development, using the data model adopted by the Gene Ontology. From its original design covering only rice, maize and Arabidopsis, the scope of the PO (...) has been expanded to include all green plants. The PO was the first multi-species anatomy ontology developed for the annotation of genes and phenotypes. Also, to our knowledge, it was one of the first biological ontologies that provides translations (via synonyms) in non-English languages such as Japanese and Spanish. There are about 2.2 million annotations linking PO terms to over 110,000 unique data objects representing genes or gene models, proteins, RNAs, germplasm and Quantitative Traits Loci (QTLs) from 22 plant species. In this paper, we focus on the plant anatomical entity branch of the PO, describing the organizing principles, resources available to users, and examples of how the PO is integrated into other plant genomics databases and web portals. We also provide two examples of comparative analyses, demonstrating how the ontology structure and PO-annotated data can be used to discover the patterns of expression of the LEAFY (LFY) and terpene synthase (TPS) gene homologs. (shrink)

Short (“seed”) or extended base pairing between microRNAs (miRNAs) and their target RNAs enables post‐transcriptional silencing in many organisms. These interactions allow the computational prediction of potential targets. In model organisms, predicted targets are frequently validated experimentally; hence meaningful miRNA‐regulated processes are reported. However, in non‐models, these reports mostly rely on computational prediction alone. Many times, further bioinformatic analyses such as Gene Ontology (GO) enrichment are based on these in silico projections. Here such approaches are reviewed, their caveats are (...) highlighted and the ease of picking false targets from predicted lists is demonstrated. Discoveries that shed new light on how miRNAs evolved to regulate targets in various phyletic groups are discussed, in addition to the pitfalls of target identification in non‐model organisms. The goal is to prevent the misuse of bioinformatic tools, as they cannot bypass the biological understanding of miRNA–target regulation. (shrink)

A review of U. Mäki (ed.). Fact and Fiction in Economics, Cambridge: Cambridge University Press, 2003. pp. xvi 384. ISBN 0521 00957. As people interested mainly in theory, methodologists and philos...

The paper begins with a more carefully stated version of ontologically neutral (ON) logic, originally introduced in (Hailperin, 1997). A non-infinitistic semantics which includes a definition of potential infinite validity follows. It is shown, without appeal to the actual infinite, that this notion provides a necessary and sufficient condition for provability in ON logic.

Research has indicated that microRNAs (miRNAs), a special class of non-coding RNAs (ncRNAs), can perform important roles in different biological and pathological processes. miRNAs’ functions are realized by regulating their respective target genes (targets). It is thus critical to identify and analyze miRNA-target interactions for a better understanding and delineation of miRNAs’ functions. However, conventional knowledge discovery and acquisition methods have many limitations. Fortunately, semantic technologies that are based on domain ontologies can render great assistance in this regard. In our (...) previous investigations, we developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), to provide the community with common data elements and data exchange standards in the miRNA research. This paper describes (1) our continuing efforts in the OMIT ontology development and (2) the application of the OMIT to enable a semantic approach for knowledge capture of miRNA-target interactions. (shrink)

Abstract The quasispecies theory is a helpful concept in the explanation of RNA virus evolution and behaviour, with a relevant impact on methods used to fight viral diseases. It has undergone some adaptations to integrate new empirical data, especially the non-deterministic nature of mutagenesis, and the variety of behavioural motifs in cooperation, competition, communication, innovation, integration, and exaptation. Also, the consortial structure of quasispecies with complementary roles of memory genomes of minority populations better fits the empirical data than did the (...) original concept of a master sequence and its mutant spectra. The high productivity of quasispecies variants generates unique sequences that never existed before and will never exist again. In the present essay, we underline that such sequences represent really new ontological entities, not just error copies of previous ones. Their primary unique property, the incredible variant production, is suggested here as quasispecies productivity, which replaces the error-replication narrative to better fit into a new relationship between mankind and living nature in the twenty-first century. (shrink)

I discuss two uses of the concept of the morphogenetic field, a tool of the 19th century biology motivated by particular ontological views of the time, which has been re-emerging and increasingly relevant in explaining microbiological phenomena. I also consider the relation of these uses to the Central Dogma of modern biology as well as Modern Synthesis of Darwinism and genetics. An induced morphogenetic field is determined by a physical field, or it acquires a physical field?s characteristics. Such a morphogenetic (...) field presents only a weak challenge to the Central Dogma of Modern Synthesis by indirectly, albeit severely, constraining variability at the molecular level. I discuss explanations that introduce structural inheritance in ciliate protozoa, as well as the experimental evidence on which these arguments are based. The global cellular morphogenetic field is a unit of such inheritance. I discuss relevant cases of structural inheritance in ciliates that bring about internal cellular as well as functional changes and point out that DNA is absent in the cortex and that RNA controls neither intermediary nor the global level of the field. I go on to argue that utilizing knowledge of known physical fields may advance explanations and understanding of the morphogenetic field in ciliates as the unit of both development and inheritance. (shrink)

The Pfizer-BioNTech coronavirus vaccine is 90 percent effective in protecting against COVID-19. It would not have been possible without the tireless effort of Professor Katalin Karikó, a scientific innovator fitting the mold of dynamic inventor Arthur Diamond presents in his book, Openness to Creative Destruction Sustaining Innovative Dynamism. Not only did Professor Karikó persist in her beliefs in the therapeutic potential of synthetic messenger RNA over the course of four decades, but she did so despite the criticisms of other scientists (...) and despite lack of financial backing for large parts of her career. Professor Karikó is a good example of the unconventional picture that Diamond paints of entrepreneurs in a specific version of market capitalism he terms, innovative dynamism. Specifically, she is an example of someone who does not hold prevailing academic theories in too high a regard and instead privileges her tacit knowledge (knowledge gained from years of working with mRNA in the lab) to persist believing in the potential of a therapy that now could quite literally save the world. Most surprisingly, she, like most of the entrepreneurs surveyed in the book, seem not primarily motivated by profit, though the money their projects eventually attract is integral to disseminating their creative ideas to the masses. -/- Are the many examples offered by Diamond that are similar to Professor Karikó’s story evidence against the long-standing suspicion that there is something morally damning in the self-interested motivations of innovative entrepreneurship? Is it the case that others would have inevitably pursued the cure that Karikó pursued, regardless of economic system? In light of COVID-19 and other high-pressure situations, ought we to care how we constrain the innovators who develop solutions? Diamond’s case for the economic system, innovative dynamism, seeks to answer these and other important questions concerning our political and cultural treatment of innovators and entrepreneurs. This review critically assesses his efforts. I make my case by first reviewing the major argumentative structure of the book, then I summarize and evaluate the three major themes Diamond presents in the book: (1) what is innovative dynamism and who are its competitors, (2) what are the major benefits of innovative dynamism, (3) who is the innovative entrepreneur and how do we support him or her? (shrink)

This paper follows the circuitous path of theories concerning the origins of viruses from the early years of the twentieth century until the present, considering RNA viruses in particular. I focus on three periods during which new understandings of the nature of viruses guided the construction and reconstruction of origin hypotheses. During the first part of the twentieth century, viruses were mostly viewed from within the framework of bacteriology and the discussion of origin centered on the “degenerative” or the “retrograde (...) evolution theory.” However, concomitantly, in the context of origin-of-life theorizing, the notion that viruses are vestiges of a prebiotic world was also being contemplated. In the 1960s the idea that viruses were genetic elements that “escaped” from cells became prevalent. These traditional hypotheses are being revisited nowadays by evolutionary virologists, who have placed them within a new conceptual framework that is supported by cutting-edge genomic and proteomic data. Two current, opposing scenarios of virus origin are presented. The philosophical dimensions of “revisiting” the original hypotheses are briefly discussed. (shrink)

[Stephen Yablo] The usual charge against Carnap's internal/external distinction is one of 'guilt by association with analytic/synthetic'. But it can be freed of this association, to become the distinction between statements made within make-believe games and those made outside them-or, rather, a special case of it with some claim to be called the metaphorical/literal distinction. Not even Quine considers figurative speech committal, so this turns the tables somewhat. To determine our ontological commitments, we have to ferret out all traces of (...) nonliterality in our assertions; if there is no sensible project of doing that, there is no sensible project of Quinean ontology. /// [Andre Gallois] I discuss Steve Yablo's defence of Carnap's distinction between internal and external questions. In the first section I set out what I take that distinction, as Carnap draws it, to be, and spell out a central motivation Carnap has for invoking it. In the second section I endorse, and augment, Yablo's response to Quine's arguments against Carnap. In the third section I say why Carnap's application of the distinction between internal and external questions runs into trouble. In the fourth section I spell out what I take to be Yablo's version of Carnap. In the last I say why that version is especially vulnerable to the objection raised in the second. (shrink)

The discovery of RNA interference in 1998 has made a lasting impact on biological research. Identifying the regulatory role of small RNAs changed the modes of molecular biological inquiry as well as biologists' understanding of genetic regulation. This article examines the early years of small RNA biology's success story. I query which factors had to come together so that small RNA research came into life in the blink of an eye. I primarily look at scientific repertoires as facilitators of rapid (...) scientific change. I show that for a short period of time, between the years 1998 and 2002, different model organism communities, investigative strategies, technological innovations, and research interests could be successfully aligned to take small RNA research off the ground. I discuss how the keystone discoveries were situated in specific experimental traditions and what strategies were employed to establish these discoveries as more general phenomena. Providing thus a practice-based approach of rapid scientific change, I ask how to relate the change in propositional bits of scientific knowledge with changes in scientific practice. (shrink)

Genetic variability is considered a key to the evolvability of species. The conversion of an adenosine (A) to inosine (I) in primary RNA transcripts can result in an amino acid change in the encoded protein, a change in secondary structure of the RNA, creation or destruction of a splice consensus site, or otherwise alter RNA fate. Substantial transcriptome and proteome variability is generated by A‐to‐I RNA editing through site‐selective post‐transcriptional recoding of single nucleotides. We posit that this epigenetic source of (...) phenotypic variation is an unrecognized mechanism of adaptive evolution. The genetic variation introduced through editing occurs at low evolutionary cost since predominant production of the wild‐type protein is retained. This property even allows exploration of sequence space that is inaccessible through mutation, leading to increased phenotypic plasticity and provides an evolutionary advantage for acclimatization as well as long‐term adaptation. Furthermore, continuous probing for novel RNA editing sites throughout the transcriptome is an intrinsic property of the editing machinery and represents the molecular basis for increased adaptability. We propose that higher organisms have therefore evolved to systems with increasing RNA editing activity and, as a result, to more complex systems. (shrink)

One of the distinctive features of the primate genome is the Alu element, a repetitive short interspersed element, over a million highly similar copies of which account for >10% of the genome. A direct consequence of this feature is that primates' transcriptome is highly enriched in long stable dsRNA structures, the preferred target of adenosine deaminases acting on RNAs (ADARs), which are the enzymes catalyzing A‐to‐I RNA editing. Indeed, A‐to‐I editing by ADARs is extremely abundant in primates: over a hundred (...) million editing sites exist in their genomes. However, there are few essential editing sites conserved across mammals that have maintained their editing level despite the radical change in ADAR target landscape. Here, we review and discuss the cost of having an unusual amount of dsRNA and editing in the transcriptome, as well as the opportunities it presents, which might have contributed to the accelerated evolution of the primates. (shrink)

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that (...) underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

RNA processing in Escherichia coli and some of its phages is reviewed here, with primary emphasis on rRNA and tRNA processing. Three enzymes, RNase III, RNase E and RNase P are responsible for most of the primary endonucleolytic RNA processing events. The first two are proteins, while RNase P is a ribozyme. These three enzymes have unique functions and in their absence, the cleavage events they catalyze are not performed. On the other hand a relatively large number of exonucleases participate (...) in the trimming of the 3′ ends of tRNA precursor molecules and they can substitute for each other. Primary processing is the first event that happens to the nascent RNA molecule, while in secondary RNA processing, the substrate is a product of a primary processing event. Although most RNA processing occurs in RNP particles, it seems that only in secondary RNA processing is the RNP particle required for the reaction. Bacteria and especially bacteriophages contain self‐splicing introns which in cases were probably acquired from other species. (shrink)

In his Target Article, Terrence Deacon develops simple models that assist in understanding the role of RNA in the origins of life. However, his models fail to adequately represent an important evolutionary dynamic. Central to this dynamic is the selection that impinges on RNA molecules in the context of their association with proto-metabolisms. This selection shapes the role of RNA in the emergence of life. When this evolutionary dynamic is appropriately taken into account, it predicts a role for RNA that (...) is consistent with the Managed-Metabolism Hypothesis about the origins of life, and inconsistent with Deacon’s account. (shrink)

Membranous organelles allow sub‐compartmentalization of biological processes. However, additional subcellular structures create dynamic reaction spaces without the need for membranes. Such membrane‐less organelles (MLOs) are physiologically relevant and impact development, gene expression regulation, and cellular stress responses. The phenomenon resulting in the formation of MLOs is called liquid–liquid phase separation (LLPS), and is primarily governed by the interactions of multi‐domain proteins or proteins harboring intrinsically disordered regions as well as RNA‐binding domains. Although the presence of RNAs affects the formation and (...) dissolution of MLOs, it remains unclear how the properties of RNAs exactly contribute to these effects. Here, the authors review this emerging field, and explore how particular RNA properties can affect LLPS and the behavior of MLOs. It is suggested that post‐transcriptional RNA modification systems could be contributors for dynamically modulating the assembly and dissolution of MLOs. (shrink)

The advent of deep sequencing technology has unexpectedly advanced our structural understanding of molecules composed of nucleic acids. A significant amount of progress has been made recently extrapolating the chemical methods to probe RNA structure into sequencing methods. Herein we review some of the canonical methods to analyze RNA structure, and then we outline how these have been used to probe the structure of many RNAs in parallel. The key is the transformation of structural biology problems into sequencing problems, whereby (...) sequencing power can be interpreted to understand nucleic acid proximity, nucleic acid conformation, or nucleic acid‐protein interactions. Utilizing such technologies in this way has the promise to provide novel structural insights into the mechanisms that control normal cellular physiology and provide insight into how structure could be perturbed in disease. (shrink)

The RNA polymerase of Enterobacteria senses the physiological state of the cell by interaction with signal molecules such as ppGpp and responds by altering the rate of initiation of rRNA and tRNA species so as to limit or enhance the capacity for further growth.

High‐fidelity binding of transcription factors (TFs) to DNA target sites is fundamental for proper regulation of cellular processes, as well as for the maintenance of cell identity. Recognition of cognate binding motifs in the genome is attributed by and large to the DNA binding domains of TFs. As an additional mode of conferring binding specificity, noncoding RNAs (ncRNAs) have been proposed to assist associated TFs in finding their binding sites by interacting with either DNA or RNA in the vicinity of (...) their target loci. However, a well‐documented example of such a mechanism was lacking until we recently reported that a ncRNA made by Epstein‐Barr virus uses an RNA–RNA interaction with nascent transcripts generated from the viral genome to facilitate the recruitment of an interacting TF, PAX5, to viral DNA. This proof‐of‐principle finding suggests that cellular ncRNAs may likewise function in guiding interacting TFs to chromatin target sites. (shrink)

RNA editing is a major post-transcriptional mechanism that changes specific nucleotides at the RNA level. The most common RNA editing type in humans is adenosine to inosine editing, which is mediated by ADAR enzymes. RNA editing events can not only change amino acids in proteins, but also affect the functions of non-coding RNAs such as miRNAs. Recent studies have characterized thousands of miRNA RNA editing events across different cancer types. Importantly, individual cases of miRNA editing have been reported to play (...) a role in cancer development. In this review, we summarize the current knowledge of miRNA editing in cancer, and discuss the mechanisms on how miRNA-related editing events modulate the initiation and progression of human cancer. Finally, we discuss the challenges and future directions of studying miRNA editing in cancer. RNA editing is introduced by ADAR or APOBEC enzymes, leading to specific nucleotide changes, respectively. The interplays between RNA editing and miRNAs may play important roles in cancer. This graphical abstract shows four major mechanisms through which miRNAs interact with RNA editing to confer a functional impact on tumor development. (shrink)

RNA can catalyse chemical reactions through its ability to fold into complex three‐dimensional structures and to specifically bind small molecules and divalent metal ions. The 2′‐hydroxyl groups of the ribose moieties contribute to this exceptional reactivity of RNA, compared to DNA. RNA is not only able to catalyse phosphate ester transfer reactions in ribonucleic acids, but can also show aminoacyl esterase activity, and is probably able to promote peptide bond formation. Bearing its potential for functioning both as a genome and (...) as a gene product, RNA is suitable for in vitro evolution experiments enabling the selection of molecules with new properties. The growing repertoire of RNA catalysed reactions will establish RNA as a primordial molecule in the evolution of life. (shrink)