Search publications

Transcriptome regulation by PARP13 in basal and antiviral states in human cells.

iScience · 2024 · 27(4): 109251

The RNA-binding protein PARP13 is a primary factor in the innate antiviral response, which suppresses translation and drives decay of bound viral and host RNA. PARP13 interacts with many proteins encoded by interferon-stimulated genes (ISG) to activate antiviral pathways including …

PMID 38495826 DOI ↗

LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function.

RNA (New York, N.Y.) · 2024 · 30(3): 223-239

Mitochondria-associated RNA-binding proteins (RBPs) have emerged as key contributors to mitochondrial biogenesis and homeostasis. With few examples known, we set out to identify RBPs that regulate nuclear-encoded mitochondrial mRNAs (NEMmRNAs). Our systematic analysis of RNA targets of 150 RBPs identified …

PMID 38164626 DOI ↗

Expanded palette of RNA base editors for comprehensive RBP-RNA interactome studies.

Nature communications · 2024 · 15(1): 875

RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and STAMP (surveying targets by APOBEC1 mediated profiling) utilize …

PMID 38287010 DOI ↗

FLARE: a fast and flexible workflow for identifying RNA editing foci.

BMC bioinformatics · 2023 · 24(1): 370

Fusion of RNA-binding proteins (RBPs) to RNA base-editing enzymes (such as APOBEC1 or ADAR) has emerged as a powerful tool for the discovery of RBP binding sites. However, current methods that analyze sequencing data from RNA-base editing experiments are vulnerable …

PMID 37784060 DOI ↗

Expanded palette of RNA base editors for comprehensive RBP-RNA interactome studies.

bioRxiv : the preprint server for biology · 2023

RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and STAMP (surveying targets by APOBEC1 mediated profiling) utilize …

PMID 37808757 DOI ↗

A phage nucleus-associated RNA-binding protein is required for jumbo phage infection.

bioRxiv : the preprint server for biology · 2023

Large-genome bacteriophages (jumbo phages) of the <i>Chimalliviridae</i> family assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and CRISPR/Cas nucleases. While the nuclear shell provides broad protection against host nucleases, …

PMID 37790334 DOI ↗

A super-enhancer-regulated RNA-binding protein cascade drives pancreatic cancer.

Nature communications · 2023 · 14(1): 5195

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using unbiased analyses of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, here we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that …

PMID 37673892 DOI ↗

Remodeling oncogenic transcriptomes by small molecules targeting NONO.

Nature chemical biology · 2023 · 19(7): 825-836

Much of the human proteome is involved in mRNA homeostasis, but most RNA-binding proteins lack chemical probes. Here we identify electrophilic small molecules that rapidly and stereoselectively decrease the expression of transcripts encoding the androgen receptor and its splice variants …

PMID 36864190 DOI ↗

HydRA: Deep-learning models for predicting RNA-binding capacity from protein interaction association context and protein sequence.

Molecular cell · 2023 · 83(14): 2595-2611.e11

RNA-binding proteins (RBPs) control RNA metabolism to orchestrate gene expression and, when dysfunctional, underlie human diseases. Proteome-wide discovery efforts predict thousands of RBP candidates, many of which lack canonical RNA-binding domains (RBDs). Here, we present a hybrid ensemble RBP classifier …

PMID 37421941 DOI ↗

Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling.

Nucleic acids research · 2023 · 51(12): 6461-6478

In light of the numerous studies identifying post-transcriptional regulators on the surface of the endoplasmic reticulum (ER), we asked whether there are factors that regulate compartment specific mRNA translation in human cells. Using a proteomic survey of spatially regulated polysome …

PMID 37224531 DOI ↗

Skipper analysis of eCLIP datasets enables sensitive detection of constrained translation factor binding sites.

Cell genomics · 2023 · 3(6): 100317

Technology for crosslinking and immunoprecipitation (CLIP) followed by sequencing (CLIP-seq) has identified the transcriptomic targets of hundreds of RNA-binding proteins in cells. To increase the power of existing and future CLIP-seq datasets, we introduce Skipper, an end-to-end workflow that converts …

PMID 37388912 DOI ↗

Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and regeneration.

bioRxiv : the preprint server for biology · 2023

Muscular atrophy is a mortality risk factor that happens with disuse, chronic disease, and aging. Recovery from atrophy requires changes in several cell types including muscle fibers, and satellite and immune cells. Here we show that Zfp697/ZNF697 is a damage-induced …

PMID 37398033 DOI ↗

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 ↗

Proteomic discovery of chemical probes that perturb protein complexes in human cells.

Molecular cell · 2023 · 83(10): 1725-1742.e12

Most human proteins lack chemical probes, and several large-scale and generalizable small-molecule binding assays have been introduced to address this problem. How compounds discovered in such "binding-first" assays affect protein function, nonetheless, often remains unclear. Here, we describe a "function-first" …

PMID 37084731 DOI ↗

In Vivo Screening Unveils Pervasive RNA-Binding Protein Dependencies in Leukemic Stem Cells and Identifies ELAVL1 as a Therapeutic Target.

Blood cancer discovery · 2023 · 4(3): 180-207

Acute myeloid leukemia (AML) is fueled by leukemic stem cells (LSC) whose determinants are challenging to discern from hematopoietic stem cells (HSC) or uncover by approaches focused on general cell properties. We have identified a set of RNA-binding proteins (RBP) …

PMID 36763002 DOI ↗

Programmable macromolecule-based RNA-targeting therapies to treat human neurological disorders.

RNA (New York, N.Y.) · 2023 · 29(4): 489-497

Disruptions in RNA processing play critical roles in the pathogenesis of neurological diseases. In this Perspective, we discuss recent progress in the development of RNA-targeting therapeutic modalities. We focus on progress, limitations, and opportunities in a new generation of therapies …

PMID 36693761 DOI ↗

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 ↗

RNA binding protein DDX5 restricts RORγt⁺ T_reg suppressor function to promote intestine inflammation.

Science advances · 2023 · 9(5): eadd6165

Retinoid-related orphan receptor (RAR) gamma (RORγt)-expressing regulatory T cells (RORγt⁺ T_regs) play pivotal roles in preventing T cell hyperactivation and maintaining tissue homeostasis, in part by secreting the anti-inflammation cytokine interleukin-10 (IL-10). Here, we report that hypoxia-induced factor 1α (HIF1α) …

PMID 36724232 DOI ↗

An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models.

Nature neuroscience · 2023 · 26(1): 27-38

Huntington's disease (HD) is a fatal, dominantly inherited neurodegenerative disorder caused by CAG trinucleotide expansion in exon 1 of the huntingtin (HTT) gene. Since the reduction of pathogenic mutant HTT messenger RNA is therapeutic, we developed a mutant allele-sensitive CAG^EX …

PMID 36510111 DOI ↗

Multiplexed transcriptome discovery of RNA-binding protein binding sites by antibody-barcode eCLIP.

Nature methods · 2023 · 20(1): 65-69

Ultraviolet crosslinking and immunoprecipitation (CLIP) methodologies enable the identification of RNA binding sites of RNA-binding proteins (RBPs). Despite improvements in the library preparation of RNA fragments, the enhanced CLIP (eCLIP) protocol requires 4 days of hands-on time and lacks the …

PMID 36550273 DOI ↗

Author Correction: Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma.

Nature communications · 2023 · 14(1): 136

PMID 36627300 DOI ↗

RBP Image Database: A resource for the systematic characterization of the subcellular distribution properties of human RNA binding proteins.

Nucleic acids research · 2023 · 51(D1): D1549-D1557

RNA binding proteins (RBPs) are central regulators of gene expression implicated in all facets of RNA metabolism. As such, they play key roles in cellular physiology and disease etiology. Since different steps of post-transcriptional gene expression tend to occur in …

PMID 36321651 DOI ↗

The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.

Cellular and molecular gastroenterology and hepatology · 2022 · 14(1): 35-53

Hyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy. Pre- and …

PMID 35378331 DOI ↗

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 ↗

Metadensity: a background-aware python pipeline for summarizing CLIP signals on various transcriptomic sites.

Bioinformatics advances · 2022 · 2(1): vbac083

Cross-linking and immunoprecipitation (CLIP) is a technology to map the binding sites of RNA-binding proteins (RBPs). The region where an RBP binds within RNA is often indicative of its molecular function in RNA processing. As an example, the binding sites …

PMID 36388152 DOI ↗