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Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.

Molecular cell · 2024 · 84(19): 3790-3809.e8

mRNAs interact with RNA-binding proteins (RBPs) throughout their processing and maturation. While efforts have assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware, RBP-centric PPI map …

PMID 39303721 DOI ↗

Author Correction: Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.

Nature biotechnology · 2024 · 42(9): 1467

PMID 38418649 DOI ↗

Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.

Nature biotechnology · 2024 · 42(9): 1429-1441

RNA-binding proteins (RBPs) modulate alternative splicing outcomes to determine isoform expression and cellular survival. To identify RBPs that directly drive alternative exon inclusion, we developed tethered function luciferase-based splicing reporters that provide rapid, scalable and robust readouts of exon inclusion …

PMID 38168984 DOI ↗

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

Proceedings of the National Academy of Sciences of the United States of America · 2024 · 121(34): e2319724121

Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and …

PMID 39141348 DOI ↗

High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues.

Nature communications · 2024 · 15(1): 7067

RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through …

PMID 39152130 DOI ↗

ePRINT: exonuclease assisted mapping of protein-RNA interactions.

Genome biology · 2024 · 25(1): 140

RNA-binding proteins (RBPs) regulate key aspects of RNA processing including alternative splicing, mRNA degradation and localization by physically binding RNA molecules. Current methods to map these interactions, such as CLIP, rely on purifying single proteins at a time. Our new …

PMID 38807229 DOI ↗

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

Nucleic acids research · 2024 · 52(8): 4440-4455

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

PMID 38554115 DOI ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗