Search Results (281)

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine. Full article

Acute myeloid leukemia (AML) is a malignant hematological tumor with a high prevalence in elderly people, and circular RNA (circRNA) plays an important role in age-related diseases. Induction of cancer cell senescence is a highly promising therapeutic strategy; however, the presence of senescence-associated circRNAs in AML remains to be elucidated. Here, we show that the expression patterns of circRNAs differed between elderly AML patients and healthy volunteers. circSATB1 was significantly overexpressed in elderly patients and AML cells. Knockdown of circSATB1 resulted in the inhibition of proliferation and arrest of the cell cycle in the G0/G1 phase; no effect on apoptosis or DNA integrity was observed, and precocious cellular senescence was promoted, characterized by no change in telomere length. Database analysis revealed that there may be two miRNA and nine RNA-binding proteins (RBPs) involved in regulating the cellular functions of circSATB1. Our observations uncover circSATB1-orchestrated cell senescence in AML, which provides clues for finding more modest therapeutic targets for AML. Full article

RNA-binding proteins (RBPs) are critical regulators of post-transcriptional processes, playing essential roles in nutrient metabolism and metabolic homeostasis. This literature review explores how RBPs influence the metabolism of glucose, lipid, and amino acid metabolism by controlling processes like mRNA stability and translation regulation. The dysregulation of RBPs, including HuR, PTB, and YTHDF1, is linked to metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease. Advances in techniques like TREX technology and transcriptome analysis have deepened our understanding of RBP functions. Additionally, RBPs show promise as potential biomarkers and targets for new therapies. Future research directions in RBPs could focus on tissue-specific regulation and nutrient–RBP interactions. This could pave the way for more personalized treatments and improved metabolic health. Full article

Circular RNAs (circRNAs) are single-stranded noncoding RNAs with a covalently closed loop structure. They are known for their stability, abundance, and highly conserved nature. Their expression is often specific to tissues or developmental stages. They interact with microRNAs (miRNAs) and RNA-binding proteins (RBPs) and they undergo N⁶-methyladenosine (m⁶A) modifications, further affecting gene transcription and translation. Increasing evidence over the past decades has revealed that dysregulated circRNA expression is associated with various neurological disorders, particularly the glioma, one of the most malignant tumors with a poor prognosis. Due to the presence of the blood–brain barrier (BBB) and drug resistance, conventional therapeutic approaches have shown limited efficacy. Recently, increasing attention has been directed toward precisely targeted therapies, with circRNAs emerging as promising molecules for cancer treatment. Studies indicate that circRNAs play a key role in glioma proliferation and metastasis. Substantial evidence indicates that exosomes can package circRNAs and facilitate their transport across the BBB into brain tissue, highlighting the potential of circRNAs as therapeutic targets for glioma. This review summarizes circRNAs’ functional mechanisms, clinical application relevance, and current limitations. It offers future research directions in this evolving field, aiming to encourage further research on circRNAs’ therapeutic applications and contribute to the development of novel glioma-treatment strategies. Full article

Aging in females affects the ovaries before any other organ. This has a significant impact on women’s health. Aging results in the gradual depletion of ovarian follicles and a decline in oocyte quality. Studies have shown that cellular changes within ovaries manifest before the depletion of ovarian follicles. To understand the molecular mechanisms underlying these changes, we conducted a comprehensive analysis of gene expression changes in aging mouse ovaries. When RNA sequencing data from 6-month-old mice were compared to those from 12-month-old mice, we identified numerous differentially expressed genes, as well as transcript variants. Transcript variants arise from alternative transcription start sites (TSSs) and alternative pre-mRNA processing. Therefore, we further analyzed a specific set of regulators for these cellular processes. Our findings indicate that ovarian aging alters the expression of epigenetic regulators (ERs) and transcription factors (TFs) that are involved in alternative TSS usage. Ovarian aging also affects the expression of RNA-binding proteins (RBPs) and spliceosome components (SPs), which are essential for pre-mRNA processing. We noticed that variations in transcript variants were more pronounced than those found through gene expression analysis. While 8% of the known TFs and ERs were differentially expressed at the gene level, this increased to 30% at the transcript variant level. Similarly, 3% of the known RBPs but no known SPs were differentially expressed at the gene level, while this increased to 30% at the transcript variant level. These observations highlight the importance of focusing on transcript variants and their functions in aging research, as they may provide insight into the underlying biological processes involved. Full article

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in a multitude of biological processes. However, their functional basis, particularly structure-based functional characteristics, remains elusive. lncRNAs exert their influence primarily through intricate interactions with various cellular components. Among these, interactions with proteins have garnered increasing attention. Recent research highlights the significance of the interactions with proteins as a plausible mechanism underlying lncRNA functions. Here, we delve into the interactions between lncRNAs and RNA-binding proteins (RBPs), explore their implications in cellular processes, and examine bioinformatic and experimental approaches for characterizing these interactions. We introduce an innovative ISD strategy to decipher the mysterious mechanism of lncRNAs. Through reviewing the recent advances in the study of proteins and their complexes, we incorporate the ISD strategy into our integrated structural analysis pipeline for comprehensively understanding the structure-function relationship of lncRNAs. Advances in the development of innovative therapeutic approaches based on lncRNA-protein interactions (LPIs) are reviewed accordingly. Full article

(1) RNA-binding proteins (RBPs) play a crucial role in regulating gene expression in plants, affecting growth, development, and stress responses. Accurate prediction of plant-specific RBPs is vital for understanding gene regulation and enhancing genetic improvement. (2) Methods: We propose an ensemble learning method that integrates shallow and deep learning. It integrates prediction results from SVM, LR, LDA, and LightGBM into an enhanced TextCNN, using K-Peptide Composition (KPC) encoding (k = 1, 2) to form a 420-dimensional feature vector, extended to 424 dimensions by including those four prediction outputs. Redundancy is minimized using a Pearson correlation threshold of 0.80. (3) Results: On the benchmark dataset of 4992 sequences, our method achieved an ACC of 97.20% and 97.06% under 5-fold and 10-fold cross-validation, respectively. On an independent dataset of 1086 sequences, our method attained an ACC of 99.72%, an ${\mathrm{F}1}_{\mathrm{s}\mathrm{c}\mathrm{o}\mathrm{r}\mathrm{e}}$ of 99.72%, an MCC of 99.45%, an SN of 99.63%, and an SP of 99.82%, outperforming RBPLight by 12.98 percentage points in ACC and the original TextCNN by 25.23 percentage points. (4) Conclusions: These results highlight our method’s superior accuracy and efficiency over PSSM-based approaches, enabling large-scale plant RBP prediction. Full article

Heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) is a multifunctional RNA-binding protein (RBP) that plays a central role in post-transcriptional regulation. Through its quasi-RNA recognition motifs and low-complexity domains, hnRNPH1 specifically binds guanine-rich RNA sequences, including G-quadruplex structures, to precisely modulate multiple aspects of RNA metabolism, such as alternative splicing, mRNA stability, translation, and subcellular localization. Accumulating evidence has implicated hnRNPH1 dysfunction in the pathogenesis of several human diseases. In cancer, hnRNPH1 often acts as a pro-tumorigenic factor, albeit in a context-dependent manner, influencing the alternative splicing of crucial oncogenes, mRNA stability, and tumor cell sensitivity to therapeutic agents. In the nervous system, hnRNPH1 is involved in neurodevelopment, neurodegenerative diseases, and drug addiction and plays an essential role in maintaining neuronal function and homeostasis. Furthermore, it exerts regulatory functions in reproductive system development and fertility and in non-neoplastic pathologies, including cardiovascular diseases, autoimmune disorders, and viral hepatitis. Given its pathophysiological significance, hnRNPH1 has emerged as a promising biomarker and therapeutic target. This review provides an overview of the structural basis and core molecular function of hnRNPH1. Its mechanisms of action and pathological significance in various diseases have also been detailed. Additionally, this review summarizes the current therapeutic strategies targeting hnRNPH1, discusses the associated challenges, outlines optimization approaches, and considers future research directions. Overall, this review aims to deepen our understanding of hnRNPH1 biology and inspire the development of novel diagnostic and therapeutic interventions. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is responsible for about 467,000 cancer deaths annually. An oftentimes asymptomatic early phase of this disease results in a delayed diagnosis, and patients often present with advanced disease. Current treatment options have limited survival benefits, and only a minor patient population carries actionable genomic alterations. Hence, innovative personalized treatment strategies that consider molecular, cellular and functional analyses are urgently needed for pancreatic cancer patients. However, the majority of the genetic alterations found in PDAC are currently undruggable, or patients’ response is not as expected. Therefore, non-genomic biomarkers and alternative molecular targets should be considered in order to advance the clinical management of PDAC patients. In line with this, recent gene expression and single-cell transcriptome analyses have identified molecular subtypes and transcriptional cell states that affect disease progression and drug efficiency. In this review, we will introduce long non-coding RNAs (lncRNAs) as well as RNA-binding proteins (RBPs) that are able to modulate the transcriptome of a cell through diverse mechanisms, thereby contributing to disease progression. We will provide a brief overview about the general functions of lncRNAs and RBPs, respectively. Subsequently, we will highlight selected lncRNAs and RBPs that have been shown to play a role in PDAC development, progression and drug response. Finally, we will present strategies aiming to interfere with the expression and function of lncRNAs and RBPs. Full article

Salt stress is one of the most prominent abiotic stresses. Behind the intricate adaptive responses of plants to salt stress, the regulation of gene expression assumes a pivotal role. Complementing transcriptional mechanisms, post-transcriptional regulation performed by RNA-binding proteins provides an additional layer of control through sophisticated molecular machinery. RBPs interact with both RNA molecules and protein partners to coordinate RNA metabolism and, thus, fine-tune the expression of salt-responsive genes, enabling plants to rapidly adapt to ionic challenges. This review systematically evaluates the functional roles of RBPs localized in distinct subcellular compartments, including nuclear, cytoplasmic, chloroplastic, and mitochondrial systems, in mediating post-transcriptional regulatory networks under salinity challenges. Specific classes of RBPs are discussed in detail, including glycine-rich RNA-binding proteins (GR-RBPs), serine/arginine-rich splicing factors (SR proteins), zinc finger domain-containing proteins, DEAD-box RNA helicases (DBRHs), KH domain-containing proteins, Pumilio domain-containing proteins (PUMs), pentatricopeptide repeat proteins (PPRs), and RBPs involved in cytoplasmic RNA granule formation. By integrating their subcellular localization and current mechanistic insights, this review concludes by summarizing the current knowledge and highlighting potential future research directions, aiming to inspire further investigations into the complex network of RBPs in modulating plant responses to salt stress and facilitating the development of strategies to enhance plant salt tolerance. Full article

RNA-binding proteins (RBPs) critically regulate post-transcriptional gene networks, yet their roles and mechanisms in oral squamous cell carcinoma (OSCC) remain underexplored. Dysregulated RBPs were identified through integrated analysis of RNA-seq and single-cell RNA-seq. The oncogenic functions of IGF2BP2 were evaluated through tissue microarrays, CCK-8, transwell assays, mouse xenografts, and Igf2bp2-deficient mouse models of tongue SCC (TSCC). Subsequently, we utilized RNA-seq, RIP-seq, RIP/MeRIP-qPCR, and dual-luciferase reporter assays to investigate IGF2BP2-target genes. Furthermore, cell co-culture system and mouse TSCC models were used to validate the therapeutic effect of the IGF2BP2 inhibitor. IGF2BP2 was the most markedly upregulated RBP in OSCC cells and cancer-associated fibroblasts (CAFs), correlating with unfavorable prognosis. IGF2BP2 deprivation significantly impaired human OSCC proliferation and metastasis, and delayed mouse TSCC onset. Mechanistically, IGF2BP2 stabilized EGFR and PIK3R1 mRNA via m6A-dependent interactions, thereby sustaining activation of the EGFR/PI3K/AKT oncogenic axis. Pharmacological inhibition of IGF2BP2 exhibited anti-OSCC efficacy in vivo and in vitro by concurrently suppressing EGFR and PI3K/AKT pathway activity, overcoming anti-EGFR resistance resulting from cell-intrinsic PI3K/AKT hyperactivation and CAF-secreted factors. Our findings identified IGF2BP2 as a master regulator of OSCC progression and a promising therapeutic target, offering an alternative strategy for OSCC patients suffering anti-EGFR resistance. Full article

Grafting is widely used as an effective strategy to enhance tolerance to biotic and abiotic stresses and improve fruit quality in horticultural crops. However, the molecular mechanisms of transcription and the regulatory functions in response to drought stress of mobile mRNAs remain poorly understood. In this study, we developed a grafting system based on the “one grafted plant—three samples” approach using the cultivated tomato/Solanum pennellii (Heinz 1706/LA 0716) heterografting system. A bioinformatics pipeline was developed based on RNA-seq to identify mobile mRNAs in the heterografting systems. A total of 61 upwardly and 990 downwardly mobile mRNAs were identified. Furthermore, we found that the mobility of mRNAs was not correlated with their abundance. The functional annotation and enrichment analysis indicated that mobile mRNAs were mainly involved in RNA binding, photosynthesis, photosystem, response to heat, and translation processes, and ultimately increased the drought tolerance of grafted plants. In addition, we also analyzed the RNA-binding proteins (RBPs) of downwardly mobile mRNAs and found that RBPs were conserved among species. Further, mobile mRNAs may be degraded during transportation. This study provides a pipeline for detecting mobile mRNAs in plant heterografting systems and offers new insights into future studies on long-distance mRNAs transport and regulatory mechanisms involved in drought stress responses. Full article

The growing prevalence of diabetes highlights the urgent need to study diabetic cardiovascular complications, specifically diabetic cardiomyopathy, which is a diabetes-induced myocardial dysfunction independent of hypertension or coronary artery disease. This review examines the role of mitochondrial dysfunction in promoting diabetic cardiac dysfunction and highlights metabolic mechanisms such as hyperglycaemia-induced oxidative stress. Chronic hyperglycaemia and insulin resistance can activate harmful pathways, including advanced glycation end-products (AGEs), protein kinase C (PKC) and hexosamine signalling, uncontrolled reactive oxygen species (ROS) production and mishandling of Ca²⁺ transient. These processes lead to cardiomyocyte apoptosis, fibrosis and contractile dysfunction. Moreover, endoplasmic reticulum (ER) stress and dysregulated RNA-binding proteins (RBPs) and extracellular vesicles (EVs) contribute to tissue damage, which drives cardiac function towards heart failure (HF). Advanced patient-derived induced pluripotent stem cell (iPSC) cardiac organoids (iPS-COs) are transformative tools for modelling diabetic cardiomyopathy and capturing human disease’s genetic, epigenetic and metabolic hallmarks. iPS-COs may facilitate the precise examination of molecular pathways and therapeutic interventions. Future research directions encourage the integration of advanced models with mechanistic techniques to promote novel therapeutic strategies. Full article

Reporter systems are widely used to study biomolecular interactions and processes in vivo, representing one of the basic tools used to characterize synthetic regulatory circuits. Here, we developed a method that enables the monitoring of RNA–protein interactions through a reporter system in bacteria with high temporal resolution. For this, we used a Real-Time Protein Expression Assay (RT-PEA) technology for real-time monitoring of a fluorescent reporter protein, while having bacteria growing on solid media. Experimental results were analyzed by fitting a three-variable Gompertz growth model. To validate the method, the interactions between a set of RNA sequences and the RNA-binding protein (RBP) Musashi-1 (MSI1) were evaluated, as well as the allosteric modulation of the interaction by a small molecule (oleic acid). This new approach proved to be suitable to quantitatively characterize RNA–RBP interactions, thereby expanding the toolbox to study molecular interactions in living bacteria, including allosteric modulation, with special relevance for systems that are not suitable to be studied in liquid media. Full article

In mammals, because cardiomyocytes withdraw from cell-cycle activities shortly after birth, the heart cannot repair the damage caused by a myocardial injury; thus, understanding how cardiomyocytes proliferate is among the most important topics in cardiovascular sciences. In newborn neonatal mammals, when a left ventricular injury is applied in hearts earlier than postnatal day 7, the cardiomyocytes actively proliferate and regenerate lost myocardium in the following weeks. The regulators promoting cardiomyocyte proliferation were discovered by analyzing transcriptomic data generated from models. Most of these regulators support the mRNA production of cell-cycle machinery, yet the mRNA requires translation into functional proteins under the regulation of RNA-binding proteins (RBPs). In this work, we performed a meta-analysis to study the relationship between RBP expression and cardiomyocyte proliferation. To identify RBPs associated with mouse and pig cardiomyocyte proliferation, the single-nuclei RNA sequencing (snRNA-seq) data from regenerating mouse and pig hearts were reanalyzed via an Autoencoder focusing on RBP expression. We also generated and analyzed new bulk RNA-seq from two human-induced pluripotent stem cell-derived (hiPSC) cardiomyocyte (hiPSC-CM) cell lines; the first cell line was harvested sixteen days after differentiation, when the cells still actively proliferated, and the second cell line was harvested one hundred and forty days after differentiation, when the cells ceased cell cycle activity. Then, the RBP associated with mouse, pig, and hiPSC-CM were compared across species. Twenty-one RBPs were found to be consistently upregulated, and six RBPs were downregulated in proliferating mouse, pig, and hiPSC-derived cardiomyocytes. Among upregulated RBPs across species, an immunofluorescence-based imaging analysis validated the significant increase in the proteins of DHX9, PTBP3, HNRNPUL1, and DDX6 in pig hearts with proliferating CMs. This meta-analysis in all species demonstrated a strong relationship between RBP expression and cardiomyocyte proliferation. Full article