The Exon Junction Complex Factor RBM8A in Glial Fibrillary Acid Protein-Expressing Astrocytes Modulates Locomotion Behaviors.

The role of RNA Binding Motif Protein 8a (RBM8A), an exon junction complex (EJC) component, in neurodevelopmental disorders has been increasingly studied for its crucial role in regulating multiple levels of gene expression. It regulates mRNA splicing, translation, and mRNA degradation and influences embryonic development. RBM8A protein is expressed in both neurons and astrocytes, but little is known about RBM8A's specific role in glial fibrillary acid protein (GFAP)-positive astrocytes.

Single-cell and spatial transcriptomics reveals that PTPRG activates the mA methyltransferase VIRMA to block mitophagy-mediated neuronal death in Alzheimer's disease.

Neuronal death is one of the key pathologies in Alzheimer's disease (AD). How neuronal death begins in AD is far from clear, so clarifying this process may help develop effective therapies. This study collected single-cell RNA sequencing data of 85 AD samples and 83 control samples, covering the prefrontal cortex, internal olfactory cortex, superior parietal lobe, superior frontal gyrus, caudal internal olfactory cortex, somatosensory cortex, hippocampus, superior frontal cortex and peripheral blood mononuclear cells.

Animal models of chemotherapy-induced peripheral neuropathy for hematological malignancies: A review.

Chemotherapy is one of the main treatments for hematologic malignancies. However, chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxic reactions in chemotherapy, and the occurrence of CIPN affects patients' quality of life and can cause interruption of chemotherapy in severe cases, thus reducing the efficacy of chemotherapy. We currently summarize the existing CIPN animal models, including the characteristics of several common animal models such as bortezomib-induced peripheral neuropathy, vincristine-induced peripheral neuropathy, and oxaliplatin-induced peripheral neuropathy.

Emerging role of artificial intelligence in diagnosis, classification and clinical management of glioma.

Glioma represents a dominant primary intracranial malignancy in the central nervous system. Artificial intelligence that mainly includes machine learning, and deep learning computational approaches, presents a unique opportunity to enhance clinical management of glioma through improving tumor segmentation, diagnosis, differentiation, grading, treatment, prediction of clinical outcomes (prognosis, and recurrence), molecular features, clinical classification, characterization of the tumor microenvironment, and drug discovery. A growing body of recent studies apply artificial intelligence-based models to disparate data sources of glioma, covering imaging modalities, digital pathology, high-throughput multi-omics data (especially emerging single-cell RNA sequencing and spatial transcriptome), etc.

Transcriptomic Analyses of Brains of RBM8A Conditional Knockout Mice at Different Developmental Stages Reveal Conserved Signaling Pathways Contributing to Neurodevelopmental Diseases.

RNA-binding motif 8A (RBM8A) is a core component of the exon junction complex (EJC) that binds pre-mRNAs and regulates their splicing, transport, translation, and nonsense-mediated decay (NMD). Dysfunction in the core proteins has been linked to several detriments in brain development and neuropsychiatric diseases. To understand the functional role of in brain development, we have generated brain-specific knockout mice and used next-generation RNA-sequencing to identify differentially expressed genes (DEGs) in mice with heterozygous, conditional knockout (cKO) of in the brain at postnatal day 17 (P17) and at embryonic day 12.

Diverse Roles of the Exon Junction Complex Factors in the Cell Cycle, Cancer, and Neurodevelopmental Disorders-Potential for Therapeutic Targeting.

The exon junction complex (EJC) plays a crucial role in regulating gene expression at the levels of alternative splicing, translation, mRNA localization, and nonsense-mediated decay (NMD). The EJC is comprised of three core proteins: RNA-binding motif 8A (RBM8A), Mago homolog (MAGOH), eukaryotic initiation factor 4A3 (eIF4A3), and a peripheral EJC factor, metastatic lymph node 51 (MLN51), in addition to other peripheral factors whose structural integration is activity-dependent. The physiological and mechanistic roles of the EJC in contribution to molecular, cellular, and organismal level function continue to be explored for potential insights into genetic or pathological dysfunction.

Molecular Insights and Prognosis Associated With RBM8A in Glioblastoma.

Glioblastoma (GBM) is the most invasive brain tumors, and it is associated with high rates of recurrence and mortality. The purpose of this study was to investigate the expression of RBM8A in GBM and the potential influence of its expression on the disease. Levels of RBM8A mRNA in GBM patients and controls were examined in The Cancer Genome Atlas (TCGA), GSE16011 and GSE90604 databases.

The Physiological Roles of the Exon Junction Complex in Development and Diseases.

The exon junction complex (EJC) becomes an increasingly important regulator of early gene expression in the central nervous system (CNS) and other tissues. The EJC is comprised of three core proteins: RNA-binding motif 8A (RBM8A), Mago homolog (MAGOH), eukaryotic initiation factor 4A3 (EIF4A3), and a peripheral EJC factor, metastatic lymph node 51 (MLN51), together with various auxiliary factors. The EJC is assembled specifically at exon-exon junctions on mRNAs, hence the name of the complex.

Dissecting Molecular Genetic Mechanisms of 1q21.1 CNV in Neuropsychiatric Disorders.

Pathogenic copy number variations (CNVs) contribute to the etiology of neurodevelopmental/neuropsychiatric disorders (NDs). Increased CNV burden has been found to be critically involved in NDs compared with controls in clinical studies. The 1q21.

Schizophrenia risk ZNF804A interacts with its associated proteins to modulate dendritic morphology and synaptic development.

Schizophrenia (SZ) is a devastating brain disease that affects about 1% of world population. Among the top genetic associations, zinc finger protein 804A (ZNF804A) gene encodes a zinc finger protein, associated with SZ and biolar disorder (BD). Copy number variants (CNVs) of ZNF804A have been observed in patients with autism spectrum disorders (ASDs), anxiety disorder, and BD, suggesting that ZNF804A is a dosage sensitive gene for brain development.

Full function of exon junction complex factor, Rbm8a, is critical for interneuron development.

The formation of the nervous system requires a balance between proliferation, differentiation, and migration of neural progenitors (NPs). Mutations in genes regulating development impede neurogenesis and lead to neuropsychiatric diseases, including autism spectrum disorders (ASDs) and schizophrenia (SZ). Recently, mutations in nonsense-mediated mRNA decay genes have been associated with ASDs, intellectual disability (ID), and SZ.

Rapid Size-Based Isolation of Extracellular Vesicles by Three-Dimensional Carbon Nanotube Arrays.

Recent discoveries reveal that extracellular vesicles (EVs) play an important role in transmitting signals. Although this emerging transcellular pathway enables a better understanding of neural communication, the lack of techniques for effectively isolating EVs impedes their studies. Herein, we report an emergent high-throughput platform consisting of three-dimensional carbon nanotube arrays that rapidly capture different EVs based on their sizes, without any labels.

Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A-3 gene as pivotal in hepatocellular carcinoma.

Eukaryotic initiation factor 4A-3 (EIF4A3) is a core component of the exon junction complex (EJC). Abnormalities in EIF4A3 are associated with carcinogenesis. The present study aimed to determine the biological role of EIF4A3 in hepatocellular carcinoma (HCC).

Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease.

Our previous studies revealed RBM8A may play a role in various progressive neurological diseases. The present study aimed to explore the role of RBM8A in Alzheimer's disease (AD). RBM8A is significantly down-regulated in AD.

Expression and gene regulation network of in hepatocellular carcinoma based on data mining.

RNA binding motif protein 8A (RBM8A) is an RNA binding protein in a core component of the exon junction complex. Abnormal expression is associated with carcinogenesis. We used sequencing data from the Cancer Genome Atlas database and Gene Expression Omnibus, analyzed expression and gene regulation networks in hepatocellular carcinoma (HCC).

Systematic Analysis of Gene Expression Alteration and Co-Expression Network of Eukaryotic Initiation Factor 4A-3 in Cancer.

Eukaryotic initiation factor 4A-3 (EIF4A3) is an RNA-binding protein (RBP) that is a core component of the exon junction complex (EJC). It has been identified as an important player in post-transcriptional regulation processes. Recently, investigations have focused on EIF4A3 dysfunction in carcinogenesis.

Control of CNS functions by RNA-binding proteins in neurological diseases.

Purpose Of Review: This review summarizes recent studies on the molecular mechanisms of RNA binding proteins (RBPs) that control neurological functions and pathogenesis in various neurodevelopmental and neurodegenerative diseases, including autism spectrum disorders, schizophrenia, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and spinocerebellar ataxia.

Recent Findings: RBPs are critical players in gene expression that regulate every step of posttranscriptional modifications. Recent genome-wide approaches revealed that many proteins associate with RNA, but do not contain any known RNA binding motifs.

Self-Assembly of Extracellular Vesicle-like Metal-Organic Framework Nanoparticles for Protection and Intracellular Delivery of Biofunctional Proteins.

The intracellular delivery of biofunctional enzymes or therapeutic proteins through systemic administration is of great importance in therapeutic intervention of various diseases. However, current strategies face substantial challenges owing to various biological barriers, including susceptibility to protein degradation and denaturation, poor cellular uptake, and low transduction efficiency into the cytosol. Here, we developed a biomimetic nanoparticle platform for systemic and intracellular delivery of proteins.

Light-Emitting Transition Metal Dichalcogenide Monolayers under Cellular Digestion.

2D materials cover a wide spectrum of electronic properties. Their applications are extended from electronic, optical, and chemical to biological. In terms of biomedical uses of 2D materials, the interactions between living cells and 2D materials are of paramount importance.

Displacement and hybridization reactions in aptamer-functionalized hydrogels for biomimetic protein release and signal transduction.

A variety of hydrogels have been synthesized for controlling the release of signaling molecules in applications such as drug delivery and regenerative medicine. However, it remains challenging to synthesize hydrogels with the ability to control the release of signaling molecules sequentially or periodically under physiological conditions as living cells do in response to the variation of metabolism. The purpose of this work was to study a novel biomimetic hydrogel system with the ability of recapitulating the procedure of cellular signal transduction and controlling the sequential release of signaling molecules under physiological conditions.

A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 (), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life.

Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed genome engineering in human cells.

CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome.

Transient enhancement of proliferation of neural progenitors and impairment of their long-term survival in p25 transgenic mice.

Cyclin-dependent kinase 5 (CDK5) regulates important neuronal functions via p35. p35 undergoes cleavage in response to neuronal activity and neurotoxic conditions to release its subunit p25. Although p25 has been implicated in various neurodegenerative diseases, the mechanisms by which p25 mediates neurodegenerative impairment have not been fully elucidated.

Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects.

Mutations in β-catenin (CTNNB1) have been implicated in cancer and mental disorders. Recently, loss-of-function mutations of CTNNB1 were linked to intellectual disability (ID), and rare mutations were identified in patients with autism spectrum disorder (ASD). As a key regulator of the canonical Wnt pathway, CTNNB1 plays an essential role in neurodevelopment.

A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors.

Background: Nonsense mediated mRNA decay (NMD) is an RNA surveillance mechanism that controls RNA stability and ensures the speedy degradation of erroneous and unnecessary transcripts. This mechanism depends on several core factors in the exon junction complex (EJC), eIF4A3, RBM8a, Magoh, and BTZ, as well as peripheral factors to distinguish premature stop codons (PTCs) from normal stop codons in transcripts. Recently, emerging evidence has indicated that NMD factors are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID).