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Structural and mechanistic analysis of covalent ligands targeting the RNA-binding protein NONO.

bioRxiv : the preprint server for biology · 2025

RNA-binding proteins (RBPs) play important roles in mRNA transcription, processing, and translation. Chemical tools are lacking for RBPs, which has hindered efforts to perturb and understand RBP function in cells. We recently reported a chloroacetamide compound ( <i>R</i> )-SKBG-1 that …

PMID 40661397 DOI ↗

Genome-Wide Interrogation of SARS-CoV-2 RNA-Protein Interactions Uncovers Hidden Regulatory Sites.

bioRxiv : the preprint server for biology · 2025

The global impact of the COVID-19 pandemic underscores the critical need for a comprehensive understanding of SARS-CoV-2 replication mechanisms. While the central roles of the RNA dependent RNA polymerase (NSP12), primase protein (NSP8), and nucleocapsid protein (N) in the virus …

PMID 40501555 DOI ↗

Integrative CRISPR Screens and RNA-Omics Discover an Essential Role for PUF60-3' Splice Site Interactions in Cancer Progression.

bioRxiv : the preprint server for biology · 2025

RNA-binding proteins (RBPs) are important regulators of post-transcriptional gene expression. Understanding which and how RBPs promote cancer progression is crucial for cancers that lack effective targeted therapies such as triple negative breast cancer (TNBC). Here, we employ both <i>in vitro</i> …

PMID 40655003 DOI ↗

Integrated multi-omic characterizations of the synapse reveal RNA processing factors and ubiquitin ligases associated with neurodevelopmental disorders.

Cell systems · 2025 · 16(4): 101204

The molecular composition of the excitatory synapse is incompletely defined due to its dynamic nature across developmental stages and neuronal populations. To address this gap, we apply proteomic mass spectrometry to characterize the synapse in multiple biological models, including the …

PMID 40054464 DOI ↗

Phenylpyrazoles as Inhibitors of the m⁶A RNA-Binding Protein YTHDF2.

JACS Au · 2025 · 5(2): 618-630

The <i>N</i>6-methyladenosine (m⁶A) modification, which is the most common RNA modification in eukaryotes, is regulated by the "writer" methyltransferases, the "reader" m⁶A binding proteins, and the "eraser" demethylases. m⁶A plays a multifunctional role in physiological and pathological processes, regulating all …

PMID 40017738 DOI ↗

Short 5' UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex.

bioRxiv : the preprint server for biology · 2025

Recognition of "non-self" nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5' cap structures, is critical for the innate immune response to viruses. Here, we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, …

PMID 39990370 DOI ↗

Rational design yields RNA-binding zinc finger domains with altered sequence specificity.

RNA (New York, N.Y.) · 2025 · 31(2): 150-163

Targeting and manipulating endogenous RNAs in a sequence-specific manner is essential for both understanding RNA biology and developing RNA-targeting therapeutics. RNA-binding zinc fingers (ZnFs) are excellent candidates as designer proteins to expand the RNA-targeting toolbox, due to their compact size …

PMID 39658359 DOI ↗

LARP6 regulates the mRNA translation of fibrogenic genes in liver fibrosis.

bioRxiv : the preprint server for biology · 2025

Metabolic syndrome and excessive alcohol consumption result in liver injury and fibrosis, which is characterized by increased collagen production by activated Hepatic Stellate Cells (HSCs). LARP6, an RNA-binding protein, was shown to facilitate collagen production. However, LARP6 expression and functionality …

PMID 39868246 DOI ↗

Decoding protein-RNA interactions using CLIP-based methodologies.

Nature reviews. Genetics · 2024 · 25(12): 879-895

Protein-RNA interactions are central to all RNA processing events, with pivotal roles in the regulation of gene expression and cellular functions. Dysregulation of these interactions has been increasingly linked to the pathogenesis of human diseases. High-throughput approaches to identify RNA-binding …

PMID 38982239 DOI ↗

Strategies for programmable manipulation of alternative splicing.

Current opinion in genetics & development · 2024 · 89: 102272

Alternative splicing (AS) plays a pivotal role in protein diversity and mRNA maturation. Programmable control of targeted AS events is of longstanding interest in RNA biology, promising correction of dysregulated splicing in disease and discovery of AS events. This review …

PMID 39471777 DOI ↗

Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.

Nature communications · 2024 · 15(1): 10796

Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal …

PMID 39737952 DOI ↗

Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.

Neuron · 2024 · 112(24): 4033-4047.e8

Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear …

PMID 39486415 DOI ↗

Long-read Ribo-STAMP simultaneously measures transcription and translation with isoform resolution.

Genome research · 2024 · 34(11): 2012-2024

Transcription and translation are intertwined processes in which mRNA isoforms are crucial intermediaries. However, methodological limitations in analyzing translation at the mRNA isoform level have left gaps in our understanding of critical biological processes. To address these gaps, we developed …

PMID 38906680 DOI ↗

Localized synthesis of molecular chaperones sustains neuronal proteostasis.

bioRxiv : the preprint server for biology · 2024

Neurons are challenged to maintain proteostasis in neuronal projections, particularly with the physiological stress at synapses to support intercellular communication underlying important functions such as memory and movement control. Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted …

PMID 37873158 DOI ↗

Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.

Molecular cell · 2024 · 84(19): 3826-3842.e8

RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and …

PMID 39303722 DOI ↗

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 ↗

Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.

Cell genomics · 2024 · 4(7): 100603

The uncovering of protein-RNA interactions enables a deeper understanding of RNA processing. Recent multiplexed crosslinking and immunoprecipitation (CLIP) technologies such as antibody-barcoded eCLIP (ABC) dramatically increase the throughput of mapping RNA binding protein (RBP) binding sites. However, multiplex CLIP datasets …

PMID 38955188 DOI ↗

Small nuclear RNAs enhance protein-free RNA-programmable base conversion on mammalian coding transcripts.

bioRxiv : the preprint server for biology · 2024

Endogenous U small nuclear RNAs (U snRNAs) form RNA-protein complexes responsible for eukaryotic processing of pre-mRNA into mature mRNA. Previous studies have demonstrated the utility of guide-programmable U snRNAs in targeted exon inclusion and exclusion. We investigated whether snRNAs can …

PMID 38915553 DOI ↗

circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.

bioRxiv : the preprint server for biology · 2024

Circular RNAs (circRNAs) represent a class of widespread endogenous RNAs that regulate gene expression and thereby influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses …

PMID 37745562 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 ↗