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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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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

Nature communications · 2022 · 13(1): 7506

Pediatric medulloblastoma (MB) is the most common solid malignant brain neoplasm, with Group 3 (G3) MB representing the most aggressive subgroup. MYC amplification is an independent poor prognostic factor in G3 MB, however, therapeutic targeting of the MYC pathway remains …

PMID 36473869 DOI ↗

RNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine.

Gut · 2022 · 71(9): 1790-1802

Tuft cells residing in the intestinal epithelium have diverse functions. In the small intestine, they provide protection against inflammation, combat against helminth and protist infections, and serve as entry portals for enteroviruses. In the colon, they had been implicated in …

PMID 34853057 DOI ↗

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 ↗

AKT constitutes a signal-promoted alternative exon-junction complex that regulates nonsense-mediated mRNA decay.

Molecular cell · 2022 · 82(15): 2779-2796.e10

Despite a long appreciation for the role of nonsense-mediated mRNA decay (NMD) in destroying faulty, disease-causing mRNAs and maintaining normal, physiologic mRNA abundance, additional effectors that regulate NMD activity in mammalian cells continue to be identified. Here, we describe a …

PMID 35675814 DOI ↗

MECP2-related pathways are dysregulated in a cortical organoid model of myotonic dystrophy.

Science translational medicine · 2022 · 14(651): eabn2375

Myotonic dystrophy type 1 (DM1) is a multisystem, autosomal-dominant inherited disorder caused by CTG microsatellite repeat expansions (MREs) in the 3' untranslated region of the dystrophia myotonica-protein kinase (<i>DMPK</i>) gene. Despite its prominence as the most common adult-onset muscular dystrophy, …

PMID 35767654 DOI ↗

Transcriptome-wide identification of RNA-binding protein binding sites using seCLIP-seq.

Nature protocols · 2022 · 17(5): 1223-1265

Discovery of interaction sites between RNA-binding proteins (RBPs) and their RNA targets plays a critical role in enabling our understanding of how these RBPs control RNA processing and regulation. Cross-linking and immunoprecipitation (CLIP) provides a generalizable, transcriptome-wide method by which …

PMID 35322209 DOI ↗

Nuclear and cytoplasmic poly(A) binding proteins (PABPs) favor distinct transcripts and isoforms.

Nucleic acids research · 2022 · 50(8): 4685-4702

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 …

PMID 35438785 DOI ↗

Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions.

Research square · 2022

The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral …

PMID 35313591 DOI ↗

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 ↗

Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions.

bioRxiv : the preprint server for biology · 2022

The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral …

PMID 35233578 DOI ↗

Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis.

Cellular and molecular life sciences : CMLS · 2022 · 79(3): 147

In addition to genomic alterations, aberrant changes in post-transcriptional regulation can modify gene function and drive cancer development. RNA-binding proteins (RBPs) are a large class of post-transcriptional regulators that have been increasingly implicated in carcinogenesis. By integrating multi-omics data, we …

PMID 35195778 DOI ↗

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 ↗

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 ↗

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 ↗

Non-microRNA binding competitively inhibits LIN28 regulation.

Cell reports · 2021 · 36(6): 109517

RNA binding protein (RBP) expression is finite. For RBPs that are vastly outnumbered by their potential target sites, a simple competition for binding can set the magnitude of post-transcriptional control. Here, we show that LIN28, best known for its direct …

PMID 34380031 DOI ↗