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27 results
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ESCAPE: assigning site-specific activity to covalent ligands in cells by prime editing.
bioRxiv : the preprint server for biology · 2026
Chemical proteomics has identified covalent ligands targeting cysteine residues across many hundreds of human proteins. The functional effects of these liganding events, however, remain challenging to assign at scale. Here we describe ESCAPE (Endogenous Site-specific Competition Assays using Prime Editors), …
PMID 42619774 DOI ↗
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Aberrant host mRNA partitioning in Ebola virus condensates driven by RNA folding perpetuates species-dependent interferon response.
bioRxiv : the preprint server for biology · 2026
RNA viruses form membraneless condensates in host cells to drive replication, but whether these compartments also regulate host RNAs remains unclear. Using MERFISH-based subcellular transcriptomics, we quantified cellular mRNA recruitment into Ebola virus condensates under basal and IFN-stimulated states. We …
PMID 42465340 DOI ↗
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Flipper: An advanced framework for identifying differential RNA binding behavior with eCLIP data.
bioRxiv : the preprint server for biology · 2026
Crosslinking and immunoprecipitation (CLIP) methods remain the gold standard for characterizing RNA binding protein (RBP) behavior. As a result, many researchers rely on CLIP to assess how treatments targeting RBPs alter binding patterns and regulatory activity. However, current tools for …
PMID 41959526 DOI ↗
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Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies.
bioRxiv : the preprint server for biology · 2025
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by the selective deterioration of motor neurons in the central nervous system (CNS). A key driver of this pathogenesis is nuclear loss of ALS-associated protein TDP-43, leading to mis-splicing of TDP-43 …
PMID 41573891 DOI ↗
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Dosage-sensitive <i>RBFOX2</i> autoregulation promotes cardiomyocyte differentiation by maturing the transcriptome.
bioRxiv : the preprint server for biology · 2025
Haploinsufficiency of the RNA splicing regulator, <i>RBFOX2</i> , is linked to congenital heart disease (CHD), yet its pathogenic mechanisms remain unclear. Here, we demonstrate that RBFOX2 is essential for progressing cardiomyocyte (CM) differentiation by shifting exon usage profiles to more …
PMID 41280054 DOI ↗
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KIF5A binds RNA to orchestrate synaptic mRNA localization and stress granules in ALS.
bioRxiv : the preprint server for biology · 2025
Neuronal health depends on the precise transport and local translation of mRNAs to maintain synaptic function across highly polarized cellular architecture. While kinesin motor proteins are known to mediate mRNA transport, the specificity and direct involvement of individual kinesins as …
PMID 41279899 DOI ↗
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A splice-switching antisense oligonucleotide approach for pediatric genetic epilepsies.
bioRxiv : the preprint server for biology · 2025
Variants in ion channel genes are common causes of pediatric epilepsy, often leading to intractable seizures, developmental delay and other comorbidities, which increases risk of death. Pathogenic variants in the <i>SCN8A</i> gene, which encodes a voltage-gated sodium channel critical for …
PMID 41278710 DOI ↗
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Imaging Cellular Metabolic Rewiring with SuMMIT-SRS.
bioRxiv : the preprint server for biology · 2025
Cells dynamically rewire their metabolic pathways in response to physiological and pathological cues. Such plasticity is particularly critical in neurons, stem cells, cancer cells, and immune cells, where biosynthetic demands can shift rapidly. However, current metabolic imaging techniques using isotope …
PMID 41279865 DOI ↗
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Human AUTS2 regulates neurodevelopmental pathways via dual DNA/RNA binding.
bioRxiv : the preprint server for biology · 2025
The <i>AUTS2</i> gene is implicated in neurodevelopmental and psychiatric disorders, with patient mutations leading to intellectual disability, microcephaly, and autistic behavior. While AUTS2's chromatin-and RNA-related functions are recognized, its direct binding to RNA in human neural progenitors has not been …
PMID 41278797 DOI ↗
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RNA triggers chronic stress during neuronal aging.
bioRxiv : the preprint server for biology · 2025
Neurodegenerative diseases are linked with dysregulation of the integrated stress response (ISR), which coordinates cellular homeostasis during and after stress events. Cellular stress can arise from several sources, but there is significant disagreement about which stress might contribute to aging …
PMID 40799579 DOI ↗
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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 ↗
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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 ↗
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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 ↗
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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 ↗
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Stratification of enterochromaffin cells by single-cell expression analysis.
bioRxiv : the preprint server for biology · 2025
Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine (5-HT) to mediate disparate physiological responses. However, the molecular and cellular basis …
PMID 37662229 DOI ↗
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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 ↗
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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 ↗
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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 ↗
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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 ↗
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Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted.
bioRxiv : the preprint server for biology · 2024
Tissue-resident memory CD8 T cells (T<sub>RM</sub>) kill infected cells and recruit additional immune cells to limit pathogen invasion at barrier sites. Small intestinal (SI) T<sub>RM</sub> cells consist of distinct subpopulations with higher expression of effector molecules or greater memory potential. …
PMID 38585842 DOI ↗
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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 ↗
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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 ↗
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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 ↗
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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 ↗
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Xiphoid nucleus of the midline thalamus controls cold-induced food seeking.
bioRxiv : the preprint server for biology · 2023
Maintaining body temperature is calorically expensive for endothermic animals. Mammals eat more in the cold to compensate for energy expenditure, but the neural mechanism underlying this coupling is not well understood. Through behavioral and metabolic analyses, we found that mice …
PMID 36993706 DOI ↗