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    Transcriptome plasticity describes the cellular capacity to dynamically regulate gene expression, producing diverse transcripts and expanding functional proteomic diversity beyond genomic constraints. Recent advances emphasize its regulation through nucleotide metabolism, cellular signaling pathways such as mTOR, and long noncoding RNAs. Complementing these biological insights, state-of-the-art computational tools enable in-depth profiling and interpretation of dynamic transcriptomic data. This special feature highlights these exciting developments across four comprehensive reviews.

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    CRISPR-Cas9 technology has revolutionized biotechnology by providing an efficient, precise, and versatile tool for genome editing. This RNA-guided system allows scientists to target specific DNA sequences for modification that enables a wide array of applications in basic research, medicine, and agriculture. In research, CRISPR-Cas9 accelerates functional genomic studies by providing efficient gene knockouts, knock-ins, and regulatory element modifications. In medicine, it holds transformative potential for treating genetic disorders, developing novel gene therapies, and cancer treatments. In agriculture, CRISPR-Cas9 provides the development of crops with improved yield, resilience to environmental stress, and enhanced nutritional values. Its simplicity, high specificity, and adaptability have made CRISPR-Cas9 a tool for breakthrough of modern biotechnology, opening avenues for innovations previously thought unachievable.

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    This Collection welcomes contributions discussing key metabolic pathways, emerging biomarkers, novel therapeutic targets, and the role of metabolic reprogramming on tumor progression and therapy resistance.

    Image: © Wimon / stock.adobe.com
    Open for submissions
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    This Collection focuses on innovative therapeutic strategies and candidate identification based on the mechanisms of disease pathogenesis and brain function abnormalities in refractory brain disorders, which include neurodevelopmental, neuropsychiatric, and neurological disorders.

    Image: © [M] Matthieu / stock.adobe.com
    Open for submissions
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    The discovery and characterization of regulatory RNAs have revolutionized our understanding of gene regulation. In this special issue, we present a series of review articles that delve into the complex world of regulatory RNAs. These diverse RNA molecules play critical roles in coordinating cellular functions through gene regulation. From fundamental insights to cutting-edge discoveries, this special issue illuminates the path to comprehending and harnessing the power of regulatory RNAs.

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    The chromatin architecture of mammalian genomes exhibits a complex, multilayered three-dimensional structure. The spatial folding of chromosomes and their organization in the nucleus have profound effects on gene expression and cellular function, and changes in nuclear organization affect both normal development and various diseases. Investigating the three-dimensional organization of DNA within the nucleus, along with its temporal dynamics, constitutes a primary focus of research in the 4D Nucleome Project. This special issue provides comprehensive reviews of technological advances to investigate the 3D organization of the DNA in the nucleus and the functional implication of 4D Nucleome in physiology and human disease.

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    Mucosal tissues, including the respiratory, digestive, urinary, and skin, are crucial barriers against external pathogens. Beyond their physical barrier function, mucosal membranes foster a symbiotic relationship with commensal bacteria, contributing to the body's ecological balance. The mucosal immune system plays a pivotal role in maintaining immunological homeostasis and orchestrating interactions between innate and acquired immunity. Recent research has highlighted the importance of innate lymphocytes, including innate lymphoid cells (ILCs), γδ T cells, and CD1-restricted T cells, in immune homeostasis and responses to antigens or allergens within mucosal tissues. These specialized immune cells have unique activation modes and functions, presenting opportunities for novel therapeutic interventions in immune-related diseases. This special issue aims to provide comprehensive reviews of their activation mechanisms, functions, and potential as therapeutic targets for diverse immune disorders.

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    The regulation of cell death is an important process in maintaining tissue homeostasis in organs and is associated with a variety of physiological and pathological conditions. In addition to the well-defined necrosis and apoptosis, several new types of cell death processes have been identified, such as pyroptosis, necroptosis, and ferroptosis. To develop therapeutic tools for cancer, immune diseases, infections and metabolic pathologies, it is essential to understand the role of different regulators and effectors of each cell death process. Therefore, in this special issue, we review several recent studies on the regulation of different types of cell death and their role in health and disease. We also discuss recent trends in cell death to improve our understanding of the role of different types of cell death pathways.

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    RNA therapy is defined as the use of RNA-based molecules to prevent or treat disease. As recent research has shown, the field of RNA therapy has made significant advances. In particular, the ability to target diverse genetic materials in the body and the rapid development of drugs is why we can expect to see more research efforts focused on developing RNA-based therapeutics in the future. In this special issue, we have selected some of the most important topics related to RNA therapy. We cover the latest microRNA (miRNA) therapeutics in clinical trials, the latest efforts to deliver small interfering RNAs (siRNAs) to diverse organs, the disease association of RNA fragments derived from transfer RNAs (tRNAs), and the immune response induced by messenger RNA (mRNA) vaccines, which has received much attention. The combination of research in these different areas will enable us to overcome a range of diseases that were previously difficult to treat or prevent.

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    The transcriptomic plasticity conferred by post-transcriptional regulation is a fundamental mechanism driving the diversity of proteomes in biological systems. Similar to epigenetic modifications on DNA and histone proteins, RNA is also subject to various chemical modifications, called epitranscriptomic modifications. Notably, recent studies suggested that epitranscriptomic modifications influence almost all aspects of RNA metabolism, including stability, splicing, localization, and translation, enabling precise and flexible control of gene expression. The special issue provides comprehensive reviews of technological advances to investigate the epitranscriptome and the functional contribution of epitranscriptomic regulations in different physiological contexts and the status of human diseases. Guest Editor: Ki-Jun Yoon, Korea Advanced Institute of Science and Technology (KAIST), Korea Submission Guideline: https://www.nature.com/documents/emm-gta.pdf

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    All constituents of living organisms (e.g., DNAs, RNAs, proteins, lipids, lactate, other metabolites) are in a constant state of turnover at varying rates to achieve overall “dynamic” homeostasis. This dynamic nature of metabolism of biomolecules in fully assembled living organisms cannot be accurately revealed by the measurements of static, snapshot infor¬mation (“statomics”) on metabolisms such as transcriptomics, proteomics, metabolomics, and cellular signaling cascades, which often failed to reflect actual metabolic status. Combined approaches of fluxomics and “statomics” in vivo can provide an in-depth dynamic assessment of metabolic alterations, as well as simultaneous explorations of the molecular basis for the observed kinetic responses that enables a better understanding of the metabolic status of living organism and thus leading to discovery and development of effective therapeutics. In this Special Features, the reviews are written by experts in the field of tracer methodology or fluxomics that reveals the dynamic status of metabolism in vivo and deal with the basic principles and applications of the methodologies to various metabolic research fields (e.g., protein, lipid, lactate, and other nutrient metabolism in relation to normal and pathophysiology).

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