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  1. 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 ↗

  2. Enhancing RNA base editing on mammalian transcripts with small nuclear RNAs.

    Nature chemical biology · 2025

    Endogenous uridine-rich small nuclear RNAs (U snRNAs) form RNA-protein complexes to process eukaryotic pre-mRNA into mRNA. Previous studies have demonstrated programmable U snRNA guide-targeted exon inclusion and exclusion. Here we investigated whether snRNAs can also enhance RNA base editing over …

    PMID 40968292 DOI ↗

  3. Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.

    Nature communications · 2025 · 16(1): 7690

    Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may promote neurodegeneration. Here we demonstrate that a CNS penetrant small molecule eIF2B activator inhibits the ISR in cellular models of …

    PMID 40825784 DOI ↗

  4. 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 ↗

  5. Evaluation of novel computational methods to identify RNA-binding protein footprints from structural data.

    RNA (New York, N.Y.) · 2025 · 31(8): 1103-1124

    RNA-binding proteins (RBP) play diverse roles in mRNA processing and function. However, from thousands of RBPs encoded in the human genome, a detailed molecular understanding of their interactions with RNA is available only for a small fraction. In most cases, …

    PMID 40399037 DOI ↗

  6. Human CCR4 deadenylase homolog Angel1 is a non-stop mRNA decay factor.

    RNA (New York, N.Y.) · 2025 · 31(8): 1195-1205

    Translation elongation stalls trigger mRNA decay and degradation of the nascent polypeptide via translation-dependent quality control pathways. One such pathway, non-stop mRNA decay (NSD), targets aberrant mRNAs that lack stop codons, for example, due to premature polyadenylation. Here we identify …

    PMID 40441874 DOI ↗

  7. Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress.

    Nature neuroscience · 2025 · 28(6): 1174-1184

    Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged …

    PMID 40456907 DOI ↗

  8. 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 ↗

  9. 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 ↗

  10. 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 ↗

  11. 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 ↗

  12. Foxo1 regulates intestinal tissue-resident memory CD8 T cell biology in an anatomic compartment- and context-specific manner.

    Science immunology · 2025 · 10(106): eadn1894

    Tissue-resident memory CD8 T (T<sub>RM</sub>) cells serve as a front-line defense against microbial pathogens in barrier and mucosal tissues. Accurately predicting the roles of tissue-specific transcription factors (TFs) that regulate T<sub>RM</sub> biology remains a challenge. Here, by applying integrated transcriptomic …

    PMID 40215325 DOI ↗

  13. Stratification of enterochromaffin cells by single-cell expression analysis.

    eLife · 2025 · 12

    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 to mediate disparate physiological responses. However, the molecular and cellular basis for …

    PMID 40184163 DOI ↗

  14. Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted.

    Nature · 2025 · 639(8054): 483-492

    Tissue-resident memory CD8 T (T<sub>RM</sub>) cells provide protection from infection at barrier sites. In the small intestine, T<sub>RM</sub> cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential<sup>1</sup>. …

    PMID 39843748 DOI ↗

  15. Phenylpyrazoles as Inhibitors of the m<sup>6</sup>A RNA-Binding Protein YTHDF2.

    JACS Au · 2025 · 5(2): 618-630

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

    PMID 40017738 DOI ↗

  16. 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 ↗

  17. 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 ↗

  18. 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 ↗

  19. 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 ↗

  20. Steering research on mRNA splicing in cancer towards clinical translation.

    Nature reviews. Cancer · 2024 · 24(12): 887-905

    Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome …

    PMID 39384951 DOI ↗

  21. 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 ↗

  22. 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 ↗

  23. 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 ↗

  24. 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 ↗

  25. Supra- and sub-threshold intracellular-like recording of 2D and 3D neuronal networks using nanopillar electrode arrays.

    Microsystems & nanoengineering · 2024 · 10(1): 184

    The brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron's action …

    PMID 39632788 DOI ↗