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69 results for “RNA splicing”

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  1. Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms.

    Cancer discovery · 2022 · 12(3): 836-855

    Mutations in splicing factors (SF) are the predominant class of mutations in myelodysplastic syndrome (MDS), but convergent downstream disease drivers remain elusive. To identify common direct targets of missplicing by mutant U2AF1 and SRSF2, we performed RNA sequencing and enhanced …

    PMID 34620690 DOI ↗

  2. Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.

    Molecular cell · 2022 · 82(3): 645-659.e9

    Pseudouridine is a modified nucleotide that is prevalent in human mRNAs and is dynamically regulated. Here, we investigate when in their life cycle mRNAs become pseudouridylated to illuminate the potential regulatory functions of endogenous mRNA pseudouridylation. Using single-nucleotide resolution pseudouridine …

    PMID 35051350 DOI ↗

  3. A multi-scale map of cell structure fusing protein images and interactions.

    Nature · 2021 · 600(7889): 536-542

    The cell is a multi-scale structure with modular organization across at least four orders of magnitude<sup>1</sup>. Two central approaches for mapping this structure-protein fluorescent imaging and protein biophysical association-each generate extensive datasets, but of distinct qualities and resolutions that are …

    PMID 34819669 DOI ↗

  4. 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 ↗

  5. 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 ↗

  6. ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses.

    The Journal of experimental medicine · 2021 · 218(9)

    Cytosolic double-stranded RNA (dsRNA) initiates type I IFN responses. Endogenous retroelements, notably Alu elements, constitute a source of dsRNA. Adenosine-to-inosine (A-to-I) editing by ADAR induces mismatches in dsRNA and prevents recognition by MDA5 and autoinflammation. To identify additional endogenous dsRNA …

    PMID 34297039 DOI ↗

  7. The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1.

    Nature biomedical engineering · 2021 · 5(2): 157-168

    Myotonic dystrophy type I (DM1) is a multisystemic autosomal-dominant inherited human disorder that is caused by CTG microsatellite repeat expansions (MREs) in the 3' untranslated region of DMPK. Toxic RNAs expressed from such repetitive sequences can be eliminated using CRISPR-mediated …

    PMID 32929188 DOI ↗

  8. Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program.

    Molecular cell · 2020 · 80(3): 452-469.e9

    Although TP53 is the most commonly mutated gene in human cancers, the p53-dependent transcriptional programs mediating tumor suppression remain incompletely understood. Here, to uncover critical components downstream of p53 in tumor suppression, we perform unbiased RNAi and CRISPR-Cas9-based genetic screens …

    PMID 33157015 DOI ↗

  9. A role for alternative splicing in circadian control of exocytosis and glucose homeostasis.

    Genes & development · 2020 · 34(15-16): 1089-1105

    The circadian clock is encoded by a negative transcriptional feedback loop that coordinates physiology and behavior through molecular programs that remain incompletely understood. Here, we reveal rhythmic genome-wide alternative splicing (AS) of pre-mRNAs encoding regulators of peptidergic secretion within pancreatic …

    PMID 32616519 DOI ↗

  10. A large-scale binding and functional map of human RNA-binding proteins.

    Nature · 2020 · 583(7818): 711-719

    Many proteins regulate the expression of genes by binding to specific regions encoded in the genome<sup>1</sup>. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part …

    PMID 32728246 DOI ↗

  11. Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins.

    Genome biology · 2020 · 21(1): 90

    A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis …

    PMID 32252787 DOI ↗

  12. Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription.

    Cell · 2019 · 178(1): 107-121.e18

    Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA-binding proteins (RBPs). Although multiple RBPs have been implicated in transcription control, it has remained unclear how extensively RBPs directly act on …

    PMID 31251911 DOI ↗

  13. Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.

    Neuron · 2019 · 102(2): 294-320

    RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA …

    PMID 30998900 DOI ↗

  14. Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA.

    Nature communications · 2019 · 10(1): 1338

    Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants (GVs) mediating post-transcriptional regulation. Recently, genome-wide detection of in vivo binding of RNA-binding proteins is greatly facilitated by the enhanced crosslinking and immunoprecipitation (eCLIP) method. We developed …

    PMID 30902979 DOI ↗

  15. RBP-Maps enables robust generation of splicing regulatory maps.

    RNA (New York, N.Y.) · 2019 · 25(2): 193-204

    Alternative splicing of pre-messenger RNA transcripts enables the generation of multiple protein isoforms from the same gene locus, providing a major source of protein diversity in mammalian genomes. RNA binding proteins (RBPs) bind to RNA to control splice site choice …

    PMID 30413564 DOI ↗

  16. An important class of intron retention events in human erythroblasts is regulated by cryptic exons proposed to function as splicing decoys.

    RNA (New York, N.Y.) · 2018 · 24(9): 1255-1265

    During terminal erythropoiesis, the splicing machinery in differentiating erythroblasts executes a robust intron retention (IR) program that impacts expression of hundreds of genes. We studied IR mechanisms in the <i>SF3B1</i> splicing factor gene, which expresses ∼50% of its transcripts in …

    PMID 29959282 DOI ↗

  17. Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9.

    Nucleic acids research · 2018 · 46(14): 7323-7338

    Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of …

    PMID 29733375 DOI ↗

  18. 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 ↗

  19. Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.

    Cancer discovery · 2017 · 7(4): 410-423

    Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal …

    PMID 28188128 DOI ↗

  20. Experimental and Computational Considerations in the Study of RNA-Binding Protein-RNA Interactions.

    Advances in experimental medicine and biology · 2016 · 907: 1-28

    After an RNA is transcribed, it undergoes a variety of processing steps that can change the encoded protein sequence (through alternative splicing and RNA editing), regulate the stability of the RNA, and control subcellular localization, timing, and rate of translation. …

    PMID 27256380 DOI ↗

  21. Tethered Function Assays as Tools to Elucidate the Molecular Roles of RNA-Binding Proteins.

    Advances in experimental medicine and biology · 2016 · 907: 61-88

    Dynamic regulation of RNA molecules is critical to the survival and development of cells. Messenger RNAs are transcribed in the nucleus as intron-containing pre-mRNAs and bound by RNA-binding proteins, which control their fate by regulating RNA stability, splicing, polyadenylation, translation, …

    PMID 27256382 DOI ↗

  22. RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

    Nature structural & molecular biology · 2016 · 23(12): 1101-1110

    Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions …

    PMID 27775709 DOI ↗

  23. 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 ↗

  24. 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 ↗

  25. Dysregulation of RBFOX2 Is an Early Event in Cardiac Pathogenesis of Diabetes.

    Cell reports · 2016 · 15(10): 2200-2213

    Alternative splicing (AS) defects that adversely affect gene expression and function have been identified in diabetic hearts; however, the mechanisms responsible are largely unknown. Here, we show that the RNA-binding protein RBFOX2 contributes to transcriptome changes under diabetic conditions. RBFOX2 …

    PMID 27239029 DOI ↗

Datasets 21

GSE254209 GSE · GEO

Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (eCLIP).

Homo sapiens · GPL24676

GSE254210 GSE · GEO

Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS

Homo sapiens · GPL24676

GSE254208 GSE · GEO

Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (RNA-Seq).

Homo sapiens · Illumina

GSE114922 GSE · GEO

RNA sequencing of bone marrow CD34+ hematopoietic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls

Homo sapiens · GPL20301

GSE63816 GSE · GEO

Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome

Homo sapiens · GPL11154

GSE56504 GSE · GEO

Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons

Mus musculus · GPL5188

GSE127944 GSE · GEO

In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [eCLIPseq]

Mus musculus · GPL21103

GSE127743 GSE · GEO

In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [RNA-seq]

Mus musculus · GPL18480

GSE34992 GSE · GEO

Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins (splicing arrays)

Homo sapiens · GPL15106

GSE277160 GSE · GEO

Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [RNA-seq]

Homo sapiens · GPL24676

GSE64078 GSE · GEO

ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP

Homo sapiens · GPL11154

GSE277047 GSE · GEO

Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [RBNS]

synthetic construct · GPL34014

GSE34993 GSE · GEO

Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins (CLIP-Seq)

Homo sapiens · GPL9052

GSE268963 GSE · GEO

Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [SLAM-Seq]

Homo sapiens · GPL24676

GSE34995 GSE · GEO

Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins (RNA-Seq)

Homo sapiens · GPL9115

GSE249245 GSE · GEO

Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [Cut&Run]

Homo sapiens · GPL24676

GSE157917 GSE · GEO

Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS

Homo sapiens · GPL16791

GSE249246 GSE · GEO

Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [eCLIP]

Homo sapiens · GPL24676

GSE224548 GSE · GEO

A two-step in vivo CRISPR screen unveils pervasive RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a therapeutic target

Homo sapiens · GPL18460

GSE146916 GSE · GEO

A role for alternative splicing in circadian control of insulin secretion and glucose homeostasis

Mus musculus · GPL19057

GSE277161 GSE · GEO

Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [Ribo-STAMP cell lines]

Homo sapiens · GPL24676

Analyses 2

GSE25421 Processing Pipeline

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)

GSE56504 Processing Pipeline

GSE56504 · 2 steps · GSE · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)