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Mechanistic study of the hsa_circ_0074158 binding EIF4A3 impairing sepsis-induced endothelial barrier.

BACKGROUND: Sepsis remains a major clinical challenge, characterized by high rates of morbidity, mortality, and healthcare burden. Its compl … 074158 (the mouse homolog of hsa_circ_0074158 is named circ_Ctnna1) significantly decreased CTNNA1 mRNA stability and increased endothelial hyperpermeability, while its knockdown restored barrier integrity. Mechanistically, RNA pull-down and RNA RIP assays demonstrated that hsa_circ_0074158 directly binds to the RNA-binding protein (RBP) EIF4A3, which decreases …

[Study on the Sample Preservation Temperature and Period in Circulating MicroRNA Quantification Using Spike-In Control].

MicroRNA in body fluid is called circulating microRNA and is expected to be a non-invasive stable biomarker of various diseases. In real-time RT-PCR of circulating microRNA, synthetic non-human microRNA, such as cel-miR-39, is used as spike-in control RNA instead of endogenous control RNA. Spike-in control RNA, which is added into sera or plasma just before RNA extraction, does not reflect microRNA degradation in the period between blood sampling and RNA extraction. Therefore, it is essential to prevent degradation of circulating microRNA in this period for better reproducibility of the quanti

HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products via the cGAS-STING pathway.

UNLABELLED: A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent

IGF2BP3 enhances paclitaxel resistance in bladder urothelial carcinoma by recognizing m6A-modified CENPA mRNA.

Bladder urothelial carcinoma (BUC) is associated with poor prognosis and chemoresistance. The RNA-binding protein IGF2BP3 has been implicated in the progression and drug resistance of various cancers, but its role in UC remains underexplored. This study aimed to investigate the role of IGF2BP3 in regulating CENPA mRNA stability and its contribution to UC malignancy and paclitaxel (PTX) resistance. We analyzed human BUC cell lines (UMUC3, T24) and their paclitaxel-resistant counterpart (T24/R). The interaction between IGF2BP3 and CENPA mRNA was assessed using RNA immunoprecipitation (RIP), MeRI…

Nano-enabled RNAi strategies for sustainable citrus protection against viral pathogens.

In conclusion, nanotechnology-assisted RNAi offers a promising and sustainable approach for managing citrus viral diseases through improved dsRNA stability and targeted delivery. Integration of HIGS and SIGS with advanced nanocarriers may enhance antiviral efficiency against diverse citrus pathogens. However, further studies on biosafety, large-scale application, and regulatory approval are essential for successful field implementation. Citrus production is severely constrained by virus and virus-like pathogens that reduce yield fruit quality, and orchard longevity, notably Citrus tristeza vir…

RSPO2-induced ferroptosis via PTBP1-mediated FSP1 mRNA decay suppresses breast cancer progression.

INTRODUCTION: Breast cancer is the most common malignant tumor worldwide, and its high heterogeneity limits the efficacy of current clinical … . Mechanistically, immunoprecipitation, ubiquitination assays, RNA sequencing (RNA-seq), RIP-qPCR, mRNA stability assays, and ferroptosis-related measurements (ROS, GSH, MDA, Fe2+) were employed to identify interacting proteins and downstream targets. Rescue experiments with FSP1 overexpression were conducted to validate pathway specificity. RESULTS: RSPO2 was …

RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.

RNA modifications are crucial for post-transcriptional gene regulation. Research on RNA modifications has become a novel frontier of epitran … rapeutic potential of targeting RNA-modifying enzymes. The ability of RNA modifications to improve mRNA stability and translation efficacy and decrease immunogenicity has been exploited for the clinical use of mRNA cancer vaccines. This review aims to shed light on several vital cap, tail, and internal modifications of RNA with a focus on the connection between …

Are Viral Vectors Any Good for RNAi Antiviral Therapy?

RNA interference (RNAi) represents a novel approach for alternative antiviral therapy. However, issues related to RNA delivery and stability have presented serious obstacles for obtaining good therapeutic efficacy. Viral vectors are capable of efficient delivery of RNAi as short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA). Efficacy in gene silencing for therapeutic applications against viral diseases has been demonstrated in various animal models. Rotavirus (RV) miR-7 can inhibit rotavirus replication by targeting the RV nonstructural protein 5. Viral gene silencin

circGAB1 Activates Autophagy to Promote Sepsis-Associated Acute Kidney Injury by Interacting with ELAVL1 to Activate the HMGB3/β-catenin Signaling Pathway​.

Sepsis-associated acute kidney injury (SA-AKI) represents a prevalent complication in critically ill patients, and its molecular mechanisms … ar damage, and improved renal function. Mechanistically, circGAB1 bound to ELAVL1 to enhance HMGB3 mRNA stability, thereby activating the β-catenin pathway and promoting autophagy. Overexpression of ELAVL1 or HMGB3 reversed the suppressive effects of circGAB1 knockdown on autophagy and the β-catenin pathway. circGAB1 enhances HMGB3 mRNA stability by binding to …

Post-transcriptional nature of uremia-induced downregulation of hepatic apolipoprotein A-I production.

Chronic kidney disease is associated with premature death from cardiovascular disease, which is, in part, driven by high density lipoprotein … to +293 segment of ApoA-I gene. Finally, effect of uremic and control plasma was assessed on ApoA-I RNA stability. Exposure to uremic plasma significantly reduced ApoA-I mRNA expression and ApoA-I protein production. These effects were reversed by replacing uremic plasma with normal plasma. Although no difference in ApoA-I promoter activity was found between ce …

Dynamic monomer-dimer transition regulates DNA-guided RNA cleavage by MbpAgo.

Prokaryotic Argonaute proteins (pAgos) are nucleic acid-guided endonucleases with diverse functions. Mucilaginibacter paludis Argonaute (MbpAgo) is unusual in using guide DNA (gDNA) to cleave target RNA (tgRNA), but the structural basis for this activity has been unclear. Here we present cryo-electron microscopy structures of MbpAgo in apo, binary, and ternary states at up to 2.55 Å resolution. The apo structure reveals a conserved bilobal scaffold with unique insertions in the PIWI and MID domains that stabilize the catalytic conformation. Upon gDNA binding, MbpAgo forms a dimer stabilized by

The Interactions of Tau, RNA, and Stress Granules in Neurodegenerative Disease: A Comprehensive Review.

The discovery of RNA in the late 19th century revolutionized the understanding of cell biology. Subsequent discoveries over the next six dec … tau binds RNA, facilitating the formation of pathological structures, highlights the importance of RNA stability in tauopathies. However, the dynamics and consequences of RNA-tau interactions remain unclear. This review comprehensively catalogs key findings linking tau, RNA, and stress granules. These findings are important because they could offer novel oppor …

A novel mechanism by which c-MYC is aberrantly activated by epigenetic silencing of its antisense lncRNA in colon cancer.

BACKGROUND: Proto-oncogenes are abnormally activated in nearly all types of tumors. However, the epigenetic mechanism of proto-oncogene acti … ia an RNAi mechanism. MYC-AS1 RNA bound directly to the HuR protein in the cytoplasm, enhancing the RNA stability of MYC-AS1. Furthermore, MYC-AS1 inhibited c-MYC-targeted gene LDHA expression. Unlike the well-characterized oncogenic long noncoding RNA PVT1, which is coamplified with MYC and enhances its stability, MYC-AS1 is epigenetically silenced and functio …

PTM-associated condensation of homopolymeric (poly A) RNA by MDP1.

Mycobacterial DNA-binding protein 1 (MDP1) is a histone-like protein which carries endogenous post-translational modifications (PTMs) and contributes to nucleic acid organization in Mycobacterium tuberculosis (Mtb). Our previous work using total RNA (a heterogeneous mixture of RNA substrates) established that MDP1 induces RNA condensation, but the structural diversity of total RNA makes it difficult to fully resolve protein-intrinsic condensation behavior and the interactions stabilizing the resulting condensates. To minimize substrate-dependent effects, we used polyadenylic acid (poly A) RNA

Roles of eukaryotic Lsm proteins in the regulation of mRNA function.

The eukaryotic Lsm proteins belong to the large family of Sm-like proteins, which includes members from all organisms ranging from archaebacteria to humans. The Sm and Lsm proteins typically exist as hexameric or heptameric complexes in vivo and carry out RNA-related functions. Multiple complexes made up of different combinations of Sm and Lsm proteins are known in eukaryotes and these complexes are involved in a variety of functions such as mRNA decay in the cytoplasm, mRNA and pre-mRNA decay in the nucleus, pre-mRNA splicing, replication dependent histone mRNA 3'-end processing, etc. While m

Proximity labeling puts ZFP36L1 as central hub for posttranscriptional regulation networks in T cells.

Effective T cell responses against pathogens require a rapid yet tightly controlled remodeling of the proteome, and RNA binding proteins (RBPs) are key in this process. For instance, the RBP ZFP36L1 prevents excessive protein production and thereby limits immunopathology. ZFP36L1 is primarily known to mediate mRNA decay, but it can also regulate other processes. How its mode of action relates to its interaction partners is, however, not well-understood. Here, we mapped the ZFP36L1 interactome in primary human T cells. Using proximity labeling, we identified known and new interactors that regul

Genome-wide transcriptional silencing and mRNA stabilization allow the coordinated expression of the meiotic program in mice.

The transcriptional dynamic of mammalian cells when these transit from the ubiquitous mitotic to a meiotic-specific program is key to understand this switch central to sexual reproduction. By quantifying active RNA polymerase II and nascent transcripts using single cell dataset and ethynyl-uridine pool-down with sorted cells from synchronized testes, we detailed the transcriptional activity of murine male germ cells. When spermatogonia differentiate, transcription slows down, reaching minimal activity at meiotic entry and resumes during pachytene stage. This event, we termed EMLT (for early me

Qki is an essential regulator of microglial phagocytosis in demyelination.

The mechanism underpinning the regulation of microglial phagocytosis in demyelinating diseases is unclear. Here, we showed that the Quaking … and the mRNAs of Qki targets that are involved in phagocytosis, indicating that Qki regulates their RNA stability. Both Qki depletion and inhibition of Qki target Cd36 greatly reduced the phagocytic activity of microglia and macrophages. The defective uptake and degradation of myelin debris caused by Qki depletion in microglia resulted in unresolved myelin debr …

Intron retention as a component of regulated gene expression programs.

Intron retention has long been an exemplar of regulated splicing with case studies of individual events serving as models that provided key … these studies revealed various ways in which intron retention regulates protein isoform production, RNA stability and translation efficiency, and rapid induction of expression via post-transcriptional splicing of retained introns. In this review, we highlight critical findings from these transcriptomic studies and discuss commonalties in the patterns prevalent …

Модификация РНК не позволяет расширить кодон-антикодонное взаимодействие облегчить +1 Смена рамы.

Закон о внесении изменений после записи в РНК путем стабилизации функционального соответствия РНК. Хотя их роль в декодировании генератора РНК (mRNA) хорошо установлена, менее ясно, как перенос изменений РНК (tRNA) за пределы антикодона способствует стабильности tRNA и точному синтезу белка. Отсутствие таких изменений приводит к ошибкам в переводе, в том числе к смене mRNA. Интегрировав передачу энергии одним молекулярного флуоресцентного резонанса и криогенную электронную микроскопию, мы продемонстрируем, что N1-methylguanosine (м1G) модификация в положении 37 Эшеричиа коли tRNAProL необходим

Совпадение в аннотации оригинала
RNA post-transcriptional modifications act by stabilizing the functional conformations of RNA. While their role in messenger RNA (mRNA) decoding is well established, it is less clear how transfer RNA (tRNA) modifications outside the anticodon contribute to tRNA stability and accurate protein synthesis. Absence of such modifications causes translation errors,…