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27 results for “stress”
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KIF5A binds RNA to orchestrate synaptic mRNA localization and stress granules in ALS.
bioRxiv : the preprint server for biology · 2025
Neuronal health depends on the precise transport and local translation of mRNAs to maintain synaptic function across highly polarized cellular architecture. While kinesin motor proteins are known to mediate mRNA transport, the specificity and direct involvement of individual kinesins as …
PMID 41279899 DOI ↗
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Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.
Nature communications · 2025 · 16(1): 7690
Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may promote neurodegeneration. Here we demonstrate that a CNS penetrant small molecule eIF2B activator inhibits the ISR in cellular models of …
PMID 40825784 DOI ↗
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RNA triggers chronic stress during neuronal aging.
bioRxiv : the preprint server for biology · 2025
Neurodegenerative diseases are linked with dysregulation of the integrated stress response (ISR), which coordinates cellular homeostasis during and after stress events. Cellular stress can arise from several sources, but there is significant disagreement about which stress might contribute to aging …
PMID 40799579 DOI ↗
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Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress.
Nature neuroscience · 2025 · 28(6): 1174-1184
Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged …
PMID 40456907 DOI ↗
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Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.
Nature communications · 2024 · 15(1): 10796
Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal …
PMID 39737952 DOI ↗
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Localized synthesis of molecular chaperones sustains neuronal proteostasis.
bioRxiv : the preprint server for biology · 2024
Neurons are challenged to maintain proteostasis in neuronal projections, particularly with the physiological stress at synapses to support intercellular communication underlying important functions such as memory and movement control. Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted …
PMID 37873158 DOI ↗
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Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.
Molecular cell · 2024 · 84(19): 3790-3809.e8
mRNAs interact with RNA-binding proteins (RBPs) throughout their processing and maturation. While efforts have assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware, RBP-centric PPI map …
PMID 39303721 DOI ↗
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Large-scale map of RNA binding protein interactomes across the mRNA life-cycle.
bioRxiv : the preprint server for biology · 2023
Messenger RNAs (mRNAs) interact with RNA-binding proteins (RBPs) in diverse ribonucleoprotein complexes (RNPs) during distinct life-cycle stages for their processing and maturation. While substantial attention has focused on understanding RNA regulation by assigning proteins, particularly RBPs, to specific RNA substrates, …
PMID 37333282 DOI ↗
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Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death.
Nature communications · 2023 · 14(1): 551
Regulation of RNA processing contributes profoundly to tissue development and physiology. Here, we report that serine-arginine-rich splicing factor 1 (SRSF1) is essential for hepatocyte function and survival. Although SRSF1 is mainly known for its many roles in mRNA metabolism, it …
PMID 36759613 DOI ↗
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APEX Proximity Labeling of Stress Granule Proteins.
Methods in molecular biology (Clifton, N.J.) · 2022 · 2428: 381-399
Ascorbate peroxidase (APEX)-catalyzed proximity labeling has been recently established as a robust approach to uncover localized protein environments and transient protein-protein interactions occurring across mammalian cells. This molecular tool enables improved identification of individual proteins localized to and involved in …
PMID 35171492 DOI ↗
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Aging RNA granule dynamics in neurodegeneration.
Frontiers in molecular biosciences · 2022 · 9: 991641
Disordered RNA-binding proteins and repetitive RNA sequences are the main genetic causes of several neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington's disease. Importantly, these components also seed the formation of cytoplasmic liquid-like granules, like stress granules and P bodies. …
PMID 36188213 DOI ↗
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Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis.
Acta neuropathologica · 2022 · 144(3): 413-435
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by aberrant alternative splicing (AS). Nuclear loss and cytoplasmic accumulation of the splicing factor TDP-43 in motor neurons (MN) are hallmarks of ALS at late stages of the disease. However, it …
PMID 35778567 DOI ↗
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Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies.
Nature communications · 2021 · 12(1): 6324
Mutations in the cardiac splicing factor RBM20 lead to malignant dilated cardiomyopathy (DCM). To understand the mechanism of RBM20-associated DCM, we engineered isogenic iPSCs with DCM-associated missense mutations in RBM20 as well as RBM20 knockout (KO) iPSCs. iPSC-derived engineered heart …
PMID 34732726 DOI ↗
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Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress.
Cell reports · 2021 · 36(10): 109685
Persistent cytoplasmic aggregates containing RNA binding proteins (RBPs) are central to the pathogenesis of late-onset neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). These aggregates share components, molecular mechanisms, and cellular protein quality control pathways with stress-induced RNA granules (SGs). …
PMID 34496257 DOI ↗
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Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer.
Molecular cell · 2021 · 81(15): 3048-3064.e9
RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression, and aberrant RBP-RNA interactions can promote cancer progression. Here, we interrogate the function of RBPs in cancer using pooled CRISPR-Cas9 screening and identify 57 RBP candidates with distinct roles in …
PMID 34216543 DOI ↗
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Huntington's disease mice and human brain tissue exhibit increased G3BP1 granules and TDP43 mislocalization.
The Journal of clinical investigation · 2021 · 131(12)
Chronic cellular stress associated with neurodegenerative disease can result in the persistence of stress granule (SG) structures, membraneless organelles that form in response to cellular stress. In Huntington's disease (HD), chronic expression of mutant huntingtin generates various forms of cellular …
PMID 33945510 DOI ↗
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S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD.
Proceedings of the National Academy of Sciences of the United States of America · 2021 · 118(11)
Rare genetic mutations result in aggregation and spreading of cognate proteins in neurodegenerative disorders; however, in the absence of mutation (i.e., in the vast majority of "sporadic" cases), mechanisms for protein misfolding/aggregation remain largely unknown. Here, we show environmentally induced …
PMID 33692125 DOI ↗
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Pooled CRISPR screens with imaging on microraft arrays reveals stress granule-regulatory factors.
Nature methods · 2020 · 17(6): 636-642
Genetic screens using pooled CRISPR-based approaches are scalable and inexpensive, but restricted to standard readouts, including survival, proliferation and sortable markers. However, many biologically relevant cell states involve cellular and subcellular changes that are only accessible by microscopic visualization, and …
PMID 32393832 DOI ↗
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Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD.
Neuron · 2019 · 103(5): 802-819.e11
Stress granules (SGs) form during cellular stress and are implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). To yield insights into the role of SGs in pathophysiology, we performed a high-content screen to identify small …
PMID 31272829 DOI ↗
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Active Protein Neddylation or Ubiquitylation Is Dispensable for Stress Granule Dynamics.
Cell reports · 2019 · 27(5): 1356-1363.e3
Stress granule (SG) formation is frequently accompanied by ubiquitin proteasome system (UPS) impairment and ubiquitylated protein accumulation. SGs, ubiquitin, and UPS components co-localize, but the relationship between the ubiquitin pathway and SGs has not been systematically characterized. We utilize pharmacological …
PMID 31042464 DOI ↗
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Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.
Cell · 2018 · 172(3): 590-604.e13
Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, …
PMID 29373831 DOI ↗
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Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA metabolism.
Nucleic acids research · 2017 · 45(21): 12509-12528
To counteract the breakdown of genome integrity, eukaryotic cells have developed a network of surveillance pathways to prevent and resolve DNA damage. Recent data has recognized the importance of RNA binding proteins (RBPs) in DNA damage repair (DDR) pathways. Here, …
PMID 29069457 DOI ↗
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Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.
Neuron · 2016 · 92(4): 780-795
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …
PMID 27773581 DOI ↗
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Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts.
Scientific reports · 2016 · 6: 30896
Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart …
PMID 27485310 DOI ↗
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Programmable RNA Tracking in Live Cells with CRISPR/Cas9.
Cell · 2016 · 165(2): 488-96
RNA-programmed genome editing using CRISPR/Cas9 from Streptococcus pyogenes has enabled rapid and accessible alteration of specific genomic loci in many organisms. A flexible means to target RNA would allow alteration and imaging of endogenous RNA transcripts analogous to CRISPR/Cas-based genomic …
PMID 26997482 DOI ↗
Datasets 25
Transactivation-deficient p53 Mutants in Ras-induced Cellular Senescence
Mus musculus · GPL1261
Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer
Homo sapiens · GPL20301
Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia [motor cortex]
Homo sapiens · GPL18573
Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia
Homo sapiens · GPL16791
Splicing Factor SRSF1 Deficiency in the Liver Triggers NASH-like Pathology via R-Loop Induced DNA Damage and Cell Death
Mus musculus · GPL21103
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNA-seq]
Homo sapiens · GPL24676
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [eCLIP-seq]
Mus musculus · GPL24676
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNASeq, RiboSeq]
Homo sapiens · GPL24676
Mitochondrial double-stranded RNA triggers chronic stress in aged neurons
Homo sapiens · GPL24676, GPL30173
Investigational eIF2B activator DNL343 modulates the Integrated Stress Response in Preclinical Models of TDP-43 Pathology.
Homo sapiens · GPL24676
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_small_rnaseq]
Mus musculus · GPL15520
Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress
Homo sapiens · GPL20301
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_Fibs_2]
Homo sapiens · GPL15106
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [iCLIP-seq]
Mus musculus · GPL13112
RNA-seq in neurites and soma of primary hippocampal neurons isolated from P0 or P1 mice
Mus musculus · GPL19057
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_Fibs_1]
Homo sapiens · GPL15106
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_RNA-seq_mouse_SC]
Mus musculus · GPL13112
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_iPSC_MN_Stress]
Homo sapiens · GPL17585
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_mouse_SC]
Mus musculus · GPL13185
Pooled CRISPR screens with imaging on microRaft arrays reveals stress granule-regulatory factors
Homo sapiens · GPL20301
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_eCLIP_human_iPSC_MN]
Homo sapiens · GPL16791
Large-scale map of RNA binding protein interactomes across the mRNA life-cycle
Homo sapiens · GPL24676
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_iPSC_MN_ASO]
Homo sapiens · GPL17585
Analyses 12
GSE137810 · 8 steps · GSE · code_examples
Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in … (2025)
GSE276985 · 2 steps · RIP-Seq · code_examples
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
GSE276986 · 1 step · RNA-Seq · code_examples
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
GSE277082 · 2 steps · RNA-Seq · code_examples
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
GSE281960 · 10 steps · GSE · code_examples
Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in … (2025)
GSE301408 · 3 steps · eCLIP · geo_data_processing
RNA triggers chronic stress during neuronal aging. (2025)
GSE122649 · 3 steps · RNA-Seq · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
GSE124439 · 2 steps · RNA-Seq · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
GSE157467 · 6 steps · RNA-Seq · code_examples
Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress. (2021)
GSE139815 · 2 steps · OTHER · code_examples
Pooled CRISPR screens with imaging on microraft arrays reveals stress granule-regulatory factors. (2020)
GSE86462 · 3 steps · GSE · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE36648 · 1 step · GSE · code_examples
Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome. (2012)