Dogma Of Molecular Biology Research Articles

Rewriting the Central Dogma with Synthetic Genetic Polymers.

DNA and RNA are ubiquitous molecules responsible for storage and transmission of genetic information and together comprise the central dogma of molecular biology. However, the recent emergence of synthetic genetic polymers is providing an opportunity to challenge the fundamental principles of life. Herein, we describe the ongoing attempts to rewrite the central dogma with 4'-thioDNA and 4'-thioRNA, which feature a sulfur instead of an oxygen atom in the furanose ring moiety. Using reconstituted Escherichia coli gene expression machinery, studies have shown that the genetic information conserved in 4'-thioDNA can be transcribed to 4'-thioRNA and eventually translated into protein, mirroring the processes that occur in nature. Such studies underscore the feasibility of controlling life by substances other than DNA and RNA.

Toward a theory of evolution as multilevel learning

We apply the theory of learning to physically renormalizable systems in an attempt to outline a theory of biological evolution, including the origin of life, as multilevel learning. We formulate seven fundamental principles of evolution that appear to be necessary and sufficient to render a universe observable and show that they entail the major features of biological evolution, including replication and natural selection. It is shown that these cornerstone phenomena of biology emerge from the fundamental features of learning dynamics such as the existence of a loss function, which is minimized during learning. We then sketch the theory of evolution using the mathematical framework of neural networks, which provides for detailed analysis of evolutionary phenomena. To demonstrate the potential of the proposed theoretical framework, we derive a generalized version of the Central Dogma of molecular biology by analyzing the flow of information during learning (back propagation) and predicting (forward propagation) the environment by evolving organisms. The more complex evolutionary phenomena, such as major transitions in evolution (in particular, the origin of life), have to be analyzed in the thermodynamic limit, which is described in detail in the paper by Vanchurin etal. [V. Vanchurin, Y. I. Wolf, E. V. Koonin, M. I. Katsnelson, Proc. Natl. Acad. Sci. U.S.A. 119, 10.1073/pnas.2120042119 (2022)].

Undefining life's biochemistry: implications for abiogenesis.

In the mid-twentieth century, multiple Nobel Prizes rewarded discoveries of a seemingly universal set of molecules and interactions that collectively defined the chemical basis for life. Twenty-first-century science knows that every detail of this Central Dogma of Molecular Biology can vary through either biological evolution, human engineering (synthetic biology) or both. Clearly the material, molecular basis of replicating, evolving entities can be different. There is far less clarity yet for what constitutes this set of possibilities. One approach to better understand the limits and scope of moving beyond life's central dogma comes from those who study life's origins. RNA, proteins and the genetic code that binds them each look like products of natural selection. This raises the question of what step(s) preceded these particular components? Answers here will clarify whether any discrete point in time or biochemical evolution will objectively merit the label of life's origin, or whether life unfolds seamlessly from the non-living universe.

ONCOmicroARNs y sus futuras aplicaciones farmacológicas

Since the discovery of the central dogma of Molecular Biology, ribonucleic acid (RNA) was postulated as a messenger molecule, which transmitted the information of protein synthesis from DNA, in the cell nucleus, to the cytoplasm. However, research work has shown that RNA also performs functions beyond that of acting as a messenger. Thus, today it is known that there is a large number of non-protein coding RNA molecules that play a fundamental role in the cell. MicroRNAs (miRNAs) belong to this non-protein-coding RNA and their study has revolutionized our knowledge about the functionality of RNAs. MicroRNAs are gene expression regulatory molecules that help determine when or where genes are translated into protein. As their name indicates, these molecules are composed of nucleic acids (RNA) and not protein, in contrast to previously known regulators of gene expression. Due to their small size (human genes are encoded by thousands of nucleotides and microRNAs by only twenty) and their peculiar nature, microRNAs were discovered in the human genome once it was sequenced. MicroRNAs play a fundamental role in establishing cell identity. Components of the microRNA synthesis machinery, or microRNAs per se, have been associated with human pathologies. MicroRNAs have been found to play an important role in many cellular processes that are altered in cancer, such as differentiation, proliferation, and apoptosis. Thus, genes that code for microRNAs have been found in chromosomal regions frequently gained or lost in cancer. Some microRNAs have altered expression levels in cancer and have demonstrated their ability to affect cell transformation, carcinogenesis, and metastasis by acting as oncogenes or tumor suppressors. These microRNAs that are involved in tumor development have been called onco-microRNAs, and their name gives the title to this work. We are only at the beginning of understanding the functional implications of the gain or loss of a particular microRNA in cancer, and early pharmacological applications for cancer treatment are still being tested. Despite everything, this field is providing a series of promising medical applications in the diagnosis, prognosis and treatment of cancer that could provide new tools for the medicine of the future.

Origins and demise of selfish gene theory.

The idea of The Selfish Gene, first published in 1976, grew out of the Modern Synthesis of evolutionary biology formulated by Julian Huxley in 1942, and more specifically from George Williams' Adaptation and Natu - ral Selection in 1966. It presents a severely narrowed down version of Huxley's synthesis, which developed in the 1960s following the formulation of the Cen tral Dogma of molecular biology by Francis Crick. The idea rests on three assumptions: the isolation of the genome from any influences by the soma and its development in interaction with the environment (the Weis - mann Barrier), one-way causation from DNA to proteins (The Central Dogma), and the autoreplication of DNA (Schrödinger's aperiodic crystal). All three of these assumptions have now been shown to be incorrect. The 'replicator' (DNA) is not independent of the 'vehicle', the organism itself, so that The Selfish Gene can no longer be regarded as a valid scientific hypothesis.

Traversing Excitonic and Ionic Landscapes: Reduced-Dimensionality-Inspired Design of Organometal Halide Semiconductors for Energy Applications.

At the very heart of the global semiconductor industry lies the omnipresent push for new materials discovery. New materials constantly rise and fall out of fashion in the scientific literature, with those passing an initial phase of research scrutiny becoming hotbeds of characterization and optimization efforts. Yet, innumerable hours of painstaking research have been devoted to materials that have ultimately fallen by the wayside after crossing over an indefinable threshold, whereupon historical optimism is met with newfound skepticism. Materials have to perform well, and they have to do it quickly. In the past decade, metal-halide perovskites (MHPs) have garnered widespread attention. The hegemonic view in both academic and industrial circles is that these materials could be engineered to meet the demands of the semiconductor industry. Their promise as inexpensive solar cell devices is highly attractive, and it has been nothing short of remarkable that efficiencies have risen from 3.8% in 2009 to more than 25.5% in 2021. Moreover, MHPs are poised to be revolutionary materials in more ways than one. The highest MHP LED efficiency was recently reported (23.4%), and MHPs have demonstrated promise in photodetectors, memristors, and transistors. However, the many excellent properties of MHPs are contrasted by longstanding stability and reproducibility limitations that have hindered their commercialization. Overcoming the limitations of MHPs is ultimately a materials engineering problem, which should be solved by mapping more precise relationships between structure, composition, and device performance. In 1958, Francis Crick famously developed the central dogma of molecular biology which describes the unidirectional flow of information in biological systems. In the words of Crick, "nature has devised a unique instrument in which an underlying simplicity is used to express great subtlety and versatility." In this Account, taking inspiration from the hierarchical organization of nature, we describe a hierarchical approach to materials engineering of organic metal-halide semiconductors. We demonstrate that organo-metal halide semiconductors' dimensionality, composition, and morphology dictate their optoelectronic properties and can be exploited in defining more explicit relationships between structure and function. Here, we traverse three-dimensional (3D), two-dimensional (2D), and one-dimensional (1D) organo-metal halide semiconductors, detailing the morphological and compositional differences in each and the implications that can be drawn within each domain on the engineering process. Control over ion migration pathways via morphology engineering as well as control over charge formation in organic-inorganic semiconductors is demonstrated. Fundamental insights into the amount of static and dynamic disorder in the MHP lattice are provided, which can be continuously tuned as a function of composition and morphology. Using electroabsorption spectroscopy on 2D MHPs, a disorder-induced dipole moment in the exciton proportional to the summed value of static and dynamic disorder is measured. Spectroscopic isolation of exciton features in 2D MHP electroabsorption spectra allows us to obtain precise, model-independent measurements of exciton binding energies to study the effect of chemical substitutions, such as Sn2+ → Pb2+, on the value of the exciton binding energy. Finally, we conclude that this multidimensional platform, with the aid of machine learning and robotics, will be foundational in accurately predicting structure-property-device relationships in organo-metal halide semiconductors in the future.

Ribosome dysfunction in osteoarthritis.

Purpose of reviewTranslation of genetic information encoded within mRNA molecules by ribosomes into proteins is a key part of the central dogma of molecular biology. Despite the central position of the ribosome in the translation of proteins, and considering the major proteomic changes that occur in the joint during osteoarthritis development and progression, the ribosome has received very limited attention as driver of osteoarthritis pathogenesis.Recent findingsWe provide an overview of the limited literature regarding this developing topic for the osteoarthritis field. Recent key findings that connect ribosome biogenesis and activity with osteoarthritis include: ribosomal RNA transcription, processing and maturation, ribosomal protein expression, protein translation capacity and preferential translation.SummaryThe ribosome as the central cellular protein synthesis hub is largely neglected in osteoarthritis research. Findings included in this review reveal that in osteoarthritis, ribosome aberrations have been found from early-stage ribosome biogenesis, through ribosome build-up and maturation, up to preferential translation. Classically, osteoarthritis has been explained as an imbalance between joint tissue anabolism and catabolism. We postulate that osteoarthritis can be interpreted as an acquired ribosomopathy. This hypothesis fine-tunes the dogmatic anabolism/katabolism point-of-view, and may provide novel molecular opportunities for the development of osteoarthritis disease-modifying treatments.

Advances in Non-Coding RNA Sequencing.

Non-coding RNAs (ncRNAs) comprise a set of abundant and functionally diverse RNA molecules. Since the discovery of the first ncRNA in the 1960s, ncRNAs have been shown to be involved in nearly all steps of the central dogma of molecular biology. In recent years, the pace of discovery of novel ncRNAs and their cellular roles has been greatly accelerated by high-throughput sequencing. Advances in sequencing technology, library preparation protocols as well as computational biology helped to greatly expand our knowledge of which ncRNAs exist throughout the kingdoms of life. Moreover, RNA sequencing revealed crucial roles of many ncRNAs in human health and disease. In this review, we discuss the most recent methodological advancements in the rapidly evolving field of high-throughput sequencing and how it has greatly expanded our understanding of ncRNA biology across a large number of different organisms.

Caspases Switch off the m 6 A RNA Modification Pathway to Foster the Replication of a Ubiquitous Human Tumor Virus

ABSTRACTThe methylation of RNA at the N6 position of adenosine (m6A) orchestrates multiple biological processes to control development, differentiation, and cell cycle, as well as various aspects of the virus life cycle. How the m6A RNA modification pathway is regulated to finely tune these processes remains poorly understood. Here, we discovered the m6A reader YTHDF2 as a caspase substrate via proteome-wide prediction, followed by in vitro and in vivo validations. We further demonstrated that cleavage-resistant YTHDF2 blocks, while cleavage-mimicking YTHDF2 fragments promote, the replication of a common human oncogenic virus, Epstein-Barr virus (EBV). Intriguingly, our study revealed a feedback regulation between YTHDF2 and caspase-8 via m6A modification of CASP8 mRNA and YTHDF2 cleavage during EBV replication. Further, we discovered that caspases cleave multiple components within the m6A RNA modification pathway to benefit EBV replication. Our study establishes that caspase disarming of the m6A RNA modification machinery fosters EBV replication.

Mirror-image polymerase makes mirror gene

Life can look very different in a mirror. DNA’s famous double helix normally has a right-handed twist, for example, but its reflection corkscrews the other way, forming a left-handed helix called l -DNA. Researchers at Tsinghua University have now created a set of molecular tools that could help make mirror-image biology a reality and used the tools to assemble an entire mirror gene from l -DNA ( Nat. Biotechnol. 2021, DOI: 10.1038/s41587-021-00969-6 ). Ting F. Zhu , who led the work, says it is a step on the way to creating a mirror version of the so-called central dogma of molecular biology, which describes how organisms use the information encoded in DNA. This information can be copied to another DNA molecule by replication or into RNA by transcription. RNA then acts as a template to build a protein—a process called translation, which relies on a molecular machine called the ribosome.

Morphological Group Theory of Soft Matter Structure - A New Mathematics of Natural Image Numbers

The accurate understanding and interpretation of the SARS-CoV-2 electron microscope photos (EMP) is of great significance for the scientific treatment of coronary pneumonia and precise strategy. Here I study the image mathematics and physics description of micro-images of soft matter system by the morphology group theory of material structure, and show that there is a natural image numbers equation, which can be used to describe not only the common feature of soft matter structure, but also to correct classify the states into different classes, so that to study the morphology physics for soft matter science and biology, some important basic concepts of biophysics, such as the central dogma of molecular biology, Gene sequence analysis, heuristic recognition of SARS-CoV-2 can also be newly explained and understood by the equation.

Biological bases of cancer: a proposal of minimum contents for health schools

Cancer constitutes the second most common cause of death worldwide and is expected to become the leading one, even above cardiovascular diseases. The understanding of the cellular and molecular basis of cancer has led not only to the proper development of chemotherapy but also of target therapies. Although these advances are related with improved survival rates among cancer patients, it has poorly impacted its incidences. In this regard, the lack of knowledge regarding the impact that the several carcinogenic factors and their interactions have on different types of cancers may explain at least in part the difficulties to reduce incidence rates. However, is worth noticing that in several health schools of Chilean universities, cancer does not constitute a formal course, being only partially approached during other courses, such as cell biology, internal medicine, and surgery. Thus, the aim of our work is to provide students a simple and resumed manuscript about essential topics necessary to understand the biological basis of cancer. First, the reader will find some fundamentals about human biology including the cell cycle and the central dogma of molecular biology, which offers an overview of the physiological mechanisms leading to malignant neoplasia. Then, we will provide current definitions of neoplasia, benign and malignant tumors are provided. Finally, the different stages of tumor progression will be approached to allow the understanding of cancer development. These stages include (i) initiation, (ii) promotion, and (iii) progression. For the last one, metastasis, angiogenesis, extracellular matrix degradation, migration, and immune evasion will also be addressed. This work will not consider the metabolic hypothesis of cancer.

Learning the Regulatory Code of Gene Expression.

Data-driven machine learning is the method of choice for predicting molecular phenotypes from nucleotide sequence, modeling gene expression events including protein-DNA binding, chromatin states as well as mRNA and protein levels. Deep neural networks automatically learn informative sequence representations and interpreting them enables us to improve our understanding of the regulatory code governing gene expression. Here, we review the latest developments that apply shallow or deep learning to quantify molecular phenotypes and decode the cis-regulatory grammar from prokaryotic and eukaryotic sequencing data. Our approach is to build from the ground up, first focusing on the initiating protein-DNA interactions, then specific coding and non-coding regions, and finally on advances that combine multiple parts of the gene and mRNA regulatory structures, achieving unprecedented performance. We thus provide a quantitative view of gene expression regulation from nucleotide sequence, concluding with an information-centric overview of the central dogma of molecular biology.

Development of a cell-free protein synthesis system for practical use.

Conventional cell-free protein synthesis systems had been the major platform to study the mechanism behind translating genetic information into proteins, as proven in the central dogma of molecular biology. Albeit being powerful research tools, most of the in vitro methods at the time failed to produce enough protein for practical use. Tremendous efforts were being made to overcome the limitations of in vitro translation systems, though mostly with limited success. While great knowledge was accumulated on the translation mechanism and ribosome structure, researchers rationalized that it may be impossible to fully reconstitute such a complex molecular process in a test tube. This review will examine how we have solved the difficulties holding back progress. Our newly developed cell-free protein synthesis system is based on wheat embryos and has many excellent characteristics, in addition to its high translation activity and robustness. Combined with other novel elementary technologies, we have established cell-free protein synthesis systems for practical use in research and applied sciences.

Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology.

Ever since the “great oxidation event,” Earth’s cellular life forms had to cope with the danger of reactive oxygen species (ROS) affecting the integrity of biomolecules and hampering cellular metabolism circuits. Consequently, increasing ROS levels in the biosphere represented growing stress levels and thus shaped the evolution of species. Whether the ROS were produced endogenously or exogenously, different systems evolved to remove the ROS and repair the damage they inflicted. If ROS outweigh the cell’s capacity to remove the threat, we speak of oxidative stress. The injuries through oxidative stress in cells are diverse. This article reviews the damage oxidative stress imposes on the different steps of the central dogma of molecular biology in bacteria, focusing in particular on the RNA machines involved in transcription and translation.

The use of 3-D modeling and printing to teach the central dogma of molecular biology

Molecular processes are highly complex, and are frequently difficult for high school and college students to comprehend. Because of the importance of visualization in learning, along with formative assessment of student understanding, utilization of 3D modeling software aids both educators and students alike. The activity described below required non-science majors in a college-level general education biology class to build a model of the central dogma of molecular biology and the relationships between DNA, RNA, and protein using the TinkerCad website, and describe their model in relation to the cellular processes. Examples of student work are included, along with a discussion of the application to high school students, connections to the NGSS, and future directions for the activity.

Response to Denis Noble’s Article “The Illusions of the Modern Synthesis,” Biosemiotics

The Modern Synthesis (MS) was based on Darwin’s gradualist view of evolution and early twentieth Century Mendelian and population genetics. Although early results in microbial and molecular genetics seemed to solidify MS views through the Central Dogma of Molecular Biology, accepting their basic concepts as permanent truths blinded MS proponents to the importance of incompatible discoveries in the second half of the 20th and early 21st Centuries. Discoveries based largely on the DNA record have provided a radically different view of genome complexity and biologically-mediated evolutionary change.

Molecular Research on Stress Responses in Quercus spp.: From Classical Biochemistry to Systems Biology through Omics Analysis

The genus Quercus (oak), family Fagaceae, comprises around 500 species, being one of the most important and dominant woody angiosperms in the Northern Hemisphere. Nowadays, it is threatened by environmental cues, which are either of biotic or abiotic origin. This causes tree decline, dieback, and deforestation, which can worsen in a climate change scenario. In the 21st century, biotechnology should take a pivotal role in facing this problem and proposing sustainable management and conservation strategies for forests. As a non-domesticated, long-lived species, the only plausible approach for tree breeding is exploiting the natural diversity present in this species and the selection of elite, more resilient genotypes, based on molecular markers. In this direction, it is important to investigate the molecular mechanisms of the tolerance or resistance to stresses, and the identification of genes, gene products, and metabolites related to this phenotype. This research is being performed by using classical biochemistry or the most recent omics (genomics, epigenomics, transcriptomics, proteomics, and metabolomics) approaches, which should be integrated with other physiological and morphological techniques in the Systems Biology direction. This review is focused on the current state-of-the-art of such approaches for describing and integrating the latest knowledge on biotic and abiotic stress responses in Quercus spp., with special reference to Quercus ilex, the system on which the authors have been working for the last 15 years. While biotic stress factors mainly include fungi and insects such as Phytophthora cinnamomi, Cerambyx welensii, and Operophtera brumata, abiotic stress factors include salinity, drought, waterlogging, soil pollutants, cold, heat, carbon dioxide, ozone, and ultraviolet radiation. The review is structured following the Central Dogma of Molecular Biology and the omic cascade, from DNA (genomics, epigenomics, and DNA-based markers) to metabolites (metabolomics), through mRNA (transcriptomics) and proteins (proteomics). An integrated view of the different approaches, challenges, and future directions is critically discussed.

From axiomatic systems to the Dogmatic gene and beyond

The positivistic views that dominated the early debate on the foundations of mathematics, at the beginning of the 20th century, survived the “negative results” that have shown the limits of the axiomatic approach since the 1930s. Rigour, abstraction and symbolism have been confused with formalism, based on finite strings of signs, pre-given axioms, and potentially mechanisable rewriting rules. This contributed to major clarifications in the mathematical praxes but obscured the limits of formalisms due to the exclusion of the historical creation of sense proper to any science. We expand on this sometimes fruitful confusion with some case studies. We then hint to the historical creation of sense as a component of an epistemology of mathematics. We continue with an analogy with genocentric approaches in biology, as similar positivistic views resurfaced there fifty years later. Finite sequences of letters in the DNA would completely determine ontogenesis and phylogenesis, according to the Central Dogma of molecular biology. Limits and “negative evidence” have been disregarded while searching for the “gene for” everything. Alternative perspectives require a reconstruction of the sense of history as locus for the constitution of any object of biological knowledge. In particular, the historicity of biological evolution will be understood in terms of changing phase spaces and of the role of rare events in all phylogenetic trajectories. The analysis of the evolutionary production of variability, adaptivity and ecosystemic diversity is a key component of the project we hint to, as part of a renewed relation to the biological environment.

The Role of 3'UTR of RNA Viruses on mRNA Stability and Translation Enhancement.

The central dogma of molecular biology explains the flow of genetic information from DNA to functional products such as proteins. In most cases, a linear relationship with a high correlation coefficient exists between the concentration of mRNA, the middle man, and the functional product. Untranslated regions (UTRs) of RNA form a considerable base pairing that contributes to the secondary and tertiary structures of mRNA. The interaction between the mRNA secondary structures (cis-elements), RNA-binding proteins (RBP) and miRs (trans-element) are critical determinants of mRNAs' fate and stability. Among different viral families, the positive sense (+) RNA viruses use the simplest possible strategy of replication and expression, as the same molecule functions both as a genome and mRNA. Additionally, nucleotide composition and codon usage of +RNA viruses are the closest to human codon adaptation index (CAI). Since the origin of replication of viral intermediate RNA molecules is at the 3'-end of the genome, the 3'UTR plays a role in viral RNA replication. Moreover, the messenger role of RNA likely places functional demands on the 3'UTR to serve a role typical of cellular mRNA. This article reviews the effect of 3'UTR of RNA viruses with positive sense and genomes on mRNA stability and translation improvement. A range of animal (e.g., Dengue, Sindbis, Corona and Polio) and plant (Barley yellow dwarf, Brome mosaic, Turnip crinkle, Tobacco mosaic, Cowpea mosaic and Alfalfa mosaic) viruses are examined to highlight the role of 3'UTR in viral survival and as a potential target for pharmaceutical applications.