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Структурная основа регламентации стенограмм с помощью нарождающегося элемента РНК, HK022 potRNA.

Переписка, в которой RNA полимеразы (RNAPs) производят RNA из ДНК, является первым шагом в генной экспрессии. Таким образом, она сильно регулируется либо трансэлементами, такими как белковые факторы, и/или резьбами, как конкретные последовательности на ДНК. В лямбдоидной фаге HK022 содержится резьбовое пятно, которое подавляет падение и прекращение во время транскрипции ранних фаговых генов. Протокол PotRNA осуществляет исключительно деятельность по борьбе с растлением/прекращением путем прямого взаимодействия с комплексом удлинения RNA E.coli (EC) с помощью неизвестного структурного механизма

Advances in antisense oligonucleotide treatment for cancer.

RNA therapeutics, including antisense oligonucleotides (ASOs), have emerged as a promising class of drugs, with several already approved for clinical use. To date, most approved ASO-based RNA therapies target non-malignant disorders such as neurodegenerative diseases, and only a single therapy in this class has been approved for cancer. Notably, nearly half of existing RNA therapeutics act by modulating RNA splicing. Given the growing evidence implicating aberrant RNA splicing in cancer pathogenesis, the development of ASO-based therapeutics for oncologic indications is expected to accelerate.

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… Moreover, tumor cells may undergo adaptive changes during disease progression, including alterations in splicing patterns, target gene dependencies, and RNA stability, leading to therapeutic resistance. …

Unraveling the advances of non-coding RNAs on the tumor microenvironment: innovative strategies for cancer therapies.

Non-coding RNAs (ncRNAs) are crucial molecules that do not encode proteins but play roles in regulating various biological processes. Recent research highlights that ncRNAs not only control gene expression within cells but also facilitate intercellular communication via exosomes and other carriers. This function is vital in the tumor microenvironment (TME). Our review covers the structure and functions of different ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). We examine how these ncRNAs influence tumor initiation and progression. Additionall

Revealing the pharmacological effects of Remodelin against osteosarcoma based on network pharmacology, acRIP-seq and experimental validation.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. Remodelin, an inhibitor of the N (4)-Acetylcytidine (ac4C) acetylation modifying enzyme N-acetyltransferase 10 (NAT10), has been shown to have therapeutic effects on cancer in several studies, and our previous studies have confirmed the inhibitory effect of Remodelin on OS cells, however, the mechanism of action has not yet been elucidated. We used network pharmacological analysis to quantify the therapeutic targets of Remodelin against OS. acRIP-seq and RNA-seq were performed to investigate the inhibitory activity of Remode

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… Tsai K Acetylation of cytidine residues boosts HIV-1 gene expression by increasing viral RNA stability Cell Host Microbe 2020 28 306 312.e306 10.1016/j.chom.2020.05.011 32533923 PMC7429276 5. Wang G NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression Clin. …

Insights into the role of RNA m6A modification in the metabolic process and related diseases.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperati

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… N6-methyladenosine-dependent regulation of messenger RNA stability Nature 505 7481 2014 117 120 24284625 10.1038/nature12730 PMC3877715 45 Du H. Zhao Y. He J. …

Serum hsa_circ_0087776 as a new oncologic marker for the joint diagnosis of multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy caused by abnormal proliferation of bone marrow plasma cells, which lacks diagnostic markers and has a general prognosis. At present, the understanding of its pathogenesis provides the basis for the combined diagnosis and new targeted therapy of the disease. In this study, quantitative real-time PCR was used to detect 136 MM patients and 74 healthy controls, and the clinical application value of hsa_circ_0087776 as a new tumor marker and combined diagnosis was evaluated. The results showed that the expression of hsa_circ_0087776 was significant

Vision of Life's Code: Molecular Probe Nanoarchitectonics for Deep RNA/DNA Illumination.

Visualization of RNA and DNA provides a window of opportunity for the early detection of multiple diseases and approaches to manipulate them before any pathological processes occur. However, current imaging systems often fail to meet these demands due to the need for multiple RNA and DNA chemical probes, which increases experimental complexity, reduces awareness of false positives, and limits imaging accuracy in complex biosystems. In this work, we identify the key challenges associated with using multiple probes for RNA and DNA imaging and analyze the mechanisms and performance of existing im

Research on RNA modification in disease diagnosis and prognostic biomarkers: current status and challenges.

RNA modification, as a crucial post-transcriptional regulatory mechanism, plays a pivotal role in normal physiological processes and is closely associated with the onset and progression of various human diseases. Recent studies have highlighted significant alterations in the level of RNA modifications, including m6A, m6Am, m1A, m5C, m7G, ac4C, Ψ, and A-to-I editing, across multiple diseases. These findings suggest the potential of RNA modifications and their regulatory factors as biomarkers for early disease diagnosis and prognosis. This review provides an overview of statistical methods, mach

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… This modification plays a crucial role in regulating RNA stability, export and translation. Known m5C readers include eight proteins [ 36 , 37 ]. N4-acetylcytosine The ac4C modification refers to the chemical modification resulting from acetylation at the N4 position of cytosine. …

Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.

Biomolecular condensates are membraneless assemblies that concentrate proteins, nucleic acids, and other biomolecules into dynamic cellular compartments. Liquid-liquid phase separation (LLPS) is one important route by which such condensates form, particularly when multivalent interactions generate liquid-like, reversible assemblies. However, not every condensate or disease-associated assembly should be explained solely by LLPS. In the musculoskeletal system, condensates have been linked to transcription, signal transduction, RNA metabolism, stress responses, tissue development, homeostasis, an

Aptamer Therapeutics in Cancer: Current and Future.

Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesize

Research progress on N6-methyladenosine and non-coding RNA in multiple myeloma.

N6-methyladenosine (m6A) and non-coding RNA (ncRNA) play important roles in the occurrence, development, and prognosis of multiple myeloma (MM). They not only affect stemness, growth, and apoptosis of MM cells but also intervene in MM proliferation, migration, invasion, and even drug resistance. It is also a prognostic factor for poor MM survival. Therefore, in-depth research on the mechanisms of m6A and ncRNA in MM significant for diagnosis, treatment, and prognosis of MM.

mRNA вакцины для профилактики и лечения заболеваний.

mRNA вакцины стали высокоэффективными стратегиями в области профилактики и лечения болезней, в значительной степени, хотя и не полностью благодаря их выдающимся показателям в последние годы в борьбе с глобальной чумой. COVID-19. Огромное превосходство вакцин MRNA в том, что касается их эффективности, безопасности и крупномасштабного производства, побуждает фармацевтическую промышленность и биотехнологические компании распространять их применение на различные заболевания, несмотря на несомненные проблемы в проектировании, изготовлении и способе управления. В настоящем обзоре рассматриваются тех

Lipid nanoparticles for targeted siRNA delivery - going from bench to bedside.

This review covers the basic aspects of small interfering RNA delivery by lipid nano-particles (LNPs) and elaborates on the current status of clinical trials for these systems. We briefly describe the roles of all LNP components and possible strategies for their improvement. We also focus on the current clinical trials using LNP-formulated RNA and the possible outcomes for therapy in the near future. Also, we present a critical analysis of selected clinical trials that reveals the common logic behind target selection. We address this review to a wide audience, especially to medical doctors who

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… More intricate modifications are used to increase RNA stability in conjugates, as RNA itself is less sterically protected than when enveloped by LNP. 43 In most cases, data obtained on the activity of modified siRNA in vitro are easily translated in vivo; however, in vivo toxicity and siRNA stability …

Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases.

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1-0.4% adenylate residues, especially at the beginning of 3'-UTR near the translation stop codon. The m

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… In other studies, the ALKBH5-mediated demethylation of m6A increased HS3ST3B1-IT1 RNA stability. … N6-methyladenosine-dependent regulation of messenger RNA stability Nature 2014 505 117 120 10.1038/nature12730 24284625 PMC3877715 38. Hsu P.J. Zhu Y. Ma H. Guo Y. Shi X. Liu Y. Qi M. Lu Z. Shi H. Wang J. …

RNA метилтрансферазы METTL8 устанавливает m3C32 в митохондриальном tRNASThr/Ser (UCN) для оптимизации структуры trNA и митохондриального перевода.

Модифицированные нуклеотиды в tRNA являются важными определяющими факторами сворачивания, структуры и функции. Здесь мы идентифицируем METTL8 как митохондриальный белок и активный РНК метилтрансферазы, ответственный за установку m3C32 в митохондриале человека (mt-)tRNAThr и mt-tRNAser (UCN). METTL8 имеет перекрестные связи с антикодоновой стволовой петлей (ASL) многих мт-тРНК в клетках, в связи с чем возникает вопрос о том, каким образом достигается целевая специфичность метилирования. Расчленение элементов распознавания mt-tRNA выявило наличие U34G35 и t6A37/(ms2)i6A37, которые одновременно п

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resi

The Role of Long Non-Coding RNA and microRNA Networks in Hepatocellular Carcinoma and Its Tumor Microenvironment.

Hepatocellular carcinoma (HCC) is a common liver malignancy with high morbidity and poor prognosis. Long non-coding RNAs (lncRNAs) are involved in crucial biological processes of tumorigenesis and progression, and play four major regulatory roles, namely signal, decoy, guide, and scaffold, to regulate gene expression. Through these processes, lncRNAs can target microRNAs (miRNAs) to form lncRNA and miRNA networks, which regulate cancer cell proliferation, metastasis, drug resistance, and the tumor microenvironment. Here, we summarize the multifaceted functions of lncRNA and miRNA networks in t

Trials and Tribulations of MicroRNA Therapeutics.

The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Cons

Stage-specific treatment of colorectal cancer: A microRNA-nanocomposite approach.

Colorectal cancer (CRC) is among the leading causes of cancer mortality. The lifetime risk of developing CRC is about 5% in adult males and females. CRC is usually diagnosed at an advanced stage, and at this point therapy has a limited impact on cure rates and long-term survival. Novel and/or improved CRC therapeutic options are needed. The involvement of microRNAs (miRNAs) in cancer development has been reported, and their regulation in many oncogenic pathways suggests their potent tumor suppressor action. Although miRNAs provide a promising therapeutic approach for cancer, challenges such as

Polyphenols bind G4-Quadruplex structures and act as epigenetic modifiers with anti-cancer effects.

G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contribu