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30 results for “ALS”
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Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies.
bioRxiv : the preprint server for biology · 2025
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by the selective deterioration of motor neurons in the central nervous system (CNS). A key driver of this pathogenesis is nuclear loss of ALS-associated protein TDP-43, leading to mis-splicing of TDP-43 …
PMID 41573891 DOI ↗
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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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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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Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.
Neuron · 2024 · 112(24): 4033-4047.e8
Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear …
PMID 39486415 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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Protocol to process crosslinking and immunoprecipitation data into annotated binding sites.
STAR protocols · 2024 · 5(2): 103040
Here, we present a protocol for using Skipper, a pipeline designed to process crosslinking and immunoprecipitation (CLIP) data into annotated binding sites. We describe steps for partitioning annotated transcript regions and fitting data to a beta-binomial model to call windows …
PMID 38669139 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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fSHAPE, fSHAPE-eCLIP, and SHAPE-eCLIP probe transcript regions that interact with specific proteins.
STAR protocols · 2021 · 2(3): 100762
Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) structure probing techniques characterize the secondary structure of RNA molecules, which influence their functions and interactions. A variation of SHAPE, footprinting SHAPE (fSHAPE), probes RNA in the presence and absence of protein …
PMID 34485935 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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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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Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies.
Critical reviews in biochemistry and molecular biology · 2021 · 56(1): 31-53
Dozens of incurable neurological disorders result from expansion of short repeat sequences in both coding and non-coding regions of the transcriptome. Short repeat expansions underlie microsatellite repeat expansion (MRE) disorders including myotonic dystrophy (DM1, CUG<sub>50-3,500</sub> in <i>DMPK</i>; DM2, CCTG<sub>75-11,000</sub> in …
PMID 33172304 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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Overriding FUS autoregulation in mice triggers gain-of-toxic dysfunctions in RNA metabolism and autophagy-lysosome axis.
eLife · 2019 · 8
Mutations in coding and non-coding regions of FUS cause amyotrophic lateral sclerosis (ALS). The latter mutations may exert toxicity by increasing FUS accumulation. We show here that broad expression within the nervous system of wild-type or either of two ALS-linked …
PMID 30747709 DOI ↗
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Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.
Acta neuropathologica · 2018 · 136(3): 405-423
Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched …
PMID 29881994 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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Genetic mutations in RNA-binding proteins and their roles in ALS.
Human genetics · 2017 · 136(9): 1193-1214
Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of …
PMID 28762175 DOI ↗
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Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9.
Cell · 2017 · 170(5): 899-912.e10
Microsatellite repeat expansions in DNA produce pathogenic RNA species that cause dominantly inherited diseases such as myotonic dystrophy type 1 and 2 (DM1/2), Huntington's disease, and C9orf72-linked amyotrophic lateral sclerosis (C9-ALS). Means to target these repetitive RNAs are required for …
PMID 28803727 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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From Protein-RNA Predictions toward a Peptide-RNA Code.
Molecular cell · 2016 · 64(3): 437-438
The RNA field is undergoing a renaissance, with a deluge of proteins being identified to bind RNA. Two reports now introduce proteome-wide approaches that identify the peptides that are crosslinked to RNA (Castello et al., 2016; He et al., 2016).
PMID 27814488 DOI ↗
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Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.
Nature communications · 2016 · 7: 12143
The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs …
PMID 27378374 DOI ↗
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Blurred Boundaries: The RNA Binding Protein Lin28A Is Also an Epigenetic Regulator.
Molecular cell · 2016 · 61(1): 1-2
Lin28A is best known as a post-transcriptional regulator of gene expression. In this issue, Zeng et al. (2016) show that Lin28A has an unexpected role as an epigenetic regulator of DNA.
PMID 26748607 DOI ↗
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ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP.
Nature communications · 2015 · 6: 6171
The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their …
PMID 25625564 DOI ↗
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A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.
PloS one · 2014 · 9(12): e113258
The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe …
PMID 25474699 DOI ↗
Datasets 25+
Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (eCLIP).
Homo sapiens · GPL24676
Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS
Homo sapiens · GPL24676
Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (RNA-Seq).
Homo sapiens · Illumina
RBP Footprint Grand Challenge: An evaluation of novel computational approaches to RNA-binding protein target prediction from structural data
Homo sapiens · GPL20301
Mapping CCR4-NOT recruitment elements at high resolution reveals transcriptome-wide determinants of mRNA decay
GPL18573
Mapping CCR4-NOT recruitment elements at high resolution reveals transcriptome-wide determinants of mRNA decay [miRNA-Seq]
GPL18573
Mapping CCR4-NOT recruitment elements at high resolution reveals transcriptome-wide determinants of mRNA decay [RIP-Seq]
GPL18573
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [PAS-seq]
Homo sapiens · Illumina
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [RNA-Seq]
Homo sapiens · Illumina
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [eCLIP]
Homo sapiens · Illumina
MBNL2 dysfunction in outer radial glial cells is associated with disrupted corticogenesis in congenital myotonic dystrophy [scRNA-Seq]
GPL24676
MBNL2 dysfunction in outer radial glial cells is associated with disrupted corticogenesis in congenital myotonic dystrophy [eCLIP]
GPL24676
Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells
Homo sapiens · GPL570
Gene expression analysis of TSC-tubers reveals increased expression of adhesion and inflammatory factors
Homo sapiens · GPL570
Comparing isogenic pairs of hESC and hiPSC lines reveals genetic background and reprogramming method as primary sources of transcriptional variation
Homo sapiens · GPL11154
Aging-dependent demethylation of regulatory elements correlates with chromatin state and improved insulin secretion by pancreatic β cells
Mus musculus · GPL13112
The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis
6239 · GPL19757
Disruption of human-specific synaptogenesis program in autism [RNA-seq]
9598 · GPL11154
The mRNA decay factor CAR-1 regulates axon regeneration via mitochondrial calcium dynamics
6239 · GPL13657
An In Vivo Genome-Wide CRISPR Screen Identifies the RNA-Binding Protein Staufen2 as a Key Regulator of Myeloid Leukemia
Homo sapiens · GPL16791
Defining memory-like CD8 T cells that respond to PD-1 therapy in chronic viral infection
Mus musculus · GPL1261
Identification of islet-enriched long non-coding RNAs contributing to beta-cell failure in type 2 diabetes
Mus musculus · GPL9250
Genome-wide Circadian Control of Transcription at Active Enhancers Regulates Insulin Secretion and Diabetes Risk
Mus musculus · GPL17021
Colorectal cancer susceptibility loci as predictive markers of rectal cancer prognosis after surgery
Homo sapiens · GPL13497
Integrative Genomic Analysis Reveals Widespread Enhancer Regulation by p53 in Response to DNA Damage
Mus musculus · GPL9115
Showing first 25 dataset results.
Analyses 25+
GSE290248 · 1 step · geo_data_processing
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection. (2026)
GSE290281 · 1 step · eCLIP · geo_data_processing
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection. (2026)
GSE290282 · 3 steps · RNA-seq · geo_data_processing
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection. (2026)
GSE302648 · 3 steps · geo_data_processing
High-resolution mapping of CCR4-NOT recruitment elements reveals transcriptome-wide drivers of mRNA decay. (2026)
GSE302649 · 11 steps · eCLIP · geo_data_processing
High-resolution mapping of CCR4-NOT recruitment elements reveals transcriptome-wide drivers of mRNA decay. (2026)
GSE302651 · 3 steps · geo_data_processing
High-resolution mapping of CCR4-NOT recruitment elements reveals transcriptome-wide drivers of mRNA decay. (2026)
GSE125970 · 4 steps · RNA-Seq · code_examples
Stratification of enterochromaffin cells by single-cell expression analysis. (2025)
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)
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)
GSE145480 · 11 steps · RNA-Seq · code_examples
Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling. (2024)
GSE25421 · 1 step · GSE · code_examples
Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes. (2024)
GSE121569 · 12 steps · RNA-Seq · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
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)
GSE126263 · 25 steps · RIP-Seq · code_examples
Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma. (2022)
GSE126337 · 3 steps · RNA-Seq · code_examples
Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma. (2022)
GSE134597 · 4 steps · RNA-Seq · code_examples
Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma. (2022)
GSE153264 · 3 steps · RNA-Seq · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
GSE153279 · 13 steps · OTHER · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
GSE180129 · 24 steps · RIP-Seq · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
GSE181136 · 15 steps · GSE · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
GSE181137 · 1 step · GSE · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
GSE181138 · 2 steps · GSE · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
GSE181139 · 1 step · GSE · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
GSE181140 · 24 steps · GSE · code_examples
Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. (2022)
Showing first 25 analysis results.