Search
Chemo-resistance in acute myeloid leukemia (AML) patients is driven by leukemic stem cells (LSCs) resulting in high rates of relapse and low overall survival. Here, we demonstrate that upregulation of the splicing factor, RBM17 preferentially marks and sustains LSCs and …
The poly(A)-tail appended to the 3'-end of most eukaryotic transcripts plays a key role in their stability, nuclear transport, and translation. These roles are largely mediated by Poly(A) Binding Proteins (PABPs) that coat poly(A)-tails and interact with various proteins involved …
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 …
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 …
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 …
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 …
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). …
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 …
Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to disease. At present, the full set of molecular mechanisms governing the relative …
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 …
The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (<i>NOVA1</i>) plays a key role in neural development and function. <i>NOVA1</i> also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance …
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 …
The N6-methyladenosine (m<sup>6</sup>A) modification is the most prevalent post-transcriptional mRNA modification, regulating mRNA decay and splicing. It plays a major role during normal development, differentiation, and disease progression. The modification is regulated by a set of writer, eraser, and reader …
Disorders that disrupt myelin formation during development or in adulthood, such as multiple sclerosis and peripheral neuropathies, lead to severe pathologies, illustrating myelin's crucial role in normal neural functioning. However, although our understanding of glial biology is increasing, the signals …
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 …
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 …
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 …
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 …
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 …
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 …
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 …
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 …
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 …
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 …
Comprehensive RNA-binding protein analyses using enhanced CLIP (ENCORE) [dataset2]
Comprehensive RNA-binding protein analyses using enhanced CLIP (ENCORE) [dataset1]
Single-cell and isoform-specific translational profiling of the mouse brain with long-read sequencing [scRNA-Seq, longread]
Single-cell and isoform-specific translational profiling of the mouse brain [scRNA-seq]
PUF60-Mediated Splicing Is a Key Driver of Triple Negative Breast Cancer [CRISPR]
PUF60-Mediated Splicing Is a Key Driver of Triple Negative Breast Cancer [eCLIP]
PUF60-Mediated Splicing Is a Key Driver of Triple Negative Breast Cancer [RNA-seq]
RNA-targeting Cas9 corrects molecular and physiological features in pre-clinical model of myotonic dystrophy type 1
RNA sequencing of bone marrow CD34+ hematopoietic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls
Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome
Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology
Loss of canonical splicing factor SRSF1 in hepatocytes results in acute liver injury and regeneration
Splicing Factor SRSF1 Deficiency in the Liver Triggers NASH-like Pathology via R-Loop Induced DNA Damage and Cell Death
In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [eCLIPseq]
In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [RNA-seq]
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [in_situ_STAMP]
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [eCLIP-seq ]
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [isSTAMP]
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNA-seq]
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [eCLIP-seq]
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression. (2025)
Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion. (2024)
Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion. (2024)
Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion. (2024)
Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes. (2024)
Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death. (2023)
Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death. (2023)
Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)
Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (2022)