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RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

Trends in cell biology · 2026

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging …

PMID 42711219 DOI ↗

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 ↗

Organizing research at scale: Reflections on leading multi-team scientific collaborations.

Molecular cell · 2026 · 86(3): 434-438

Collaborations are critical features of modern academic science. As biological problems get more complex, larger teams become necessary. However, there is an increased level of friction in coordinating activities and attributing credit in large-scale scientific collaborations. Simple organizational principles and …

PMID 41650944 DOI ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

Bento: a toolkit for subcellular analysis of spatial transcriptomics data.

Genome biology · 2024 · 25(1): 82

The spatial organization of molecules in a cell is essential for their functions. While current methods focus on discerning tissue architecture, cell-cell interactions, and spatial expression patterns, they are limited to the multicellular scale. We present Bento, a Python toolkit …

PMID 38566187 DOI ↗

RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1β- and RNA-dependent co-activator of osteoclast gene expression.

Molecular cell · 2023 · 83(19): 3421-3437.e11

The nuclear receptor co-repressor (NCoR) complex mediates transcriptional repression dependent on histone deacetylation by histone deacetylase 3 (HDAC3) as a component of the complex. Unexpectedly, we found that signaling by the receptor activator of nuclear factor κB (RANK) converts the …

PMID 37751740 DOI ↗

Early transcriptional and epigenetic divergence of CD8+ T cells responding to acute versus chronic infection.

PLoS biology · 2023 · 21(1): e3001983

During a microbial infection, responding CD8+ T cells give rise to effector cells that provide acute host defense and memory cells that provide sustained protection. An alternative outcome is exhaustion, a state of T cell dysfunction that occurs in the …

PMID 36716323 DOI ↗

Antibody-Oligonucleotide Conjugation Using a SPAAC Copper-Free Method Compatible with 10× Genomics' Single-Cell RNA-Seq.

Methods in molecular biology (Clifton, N.J.) · 2022 · 2463: 67-80

Recent advances in multimodal approaches toward single-cell analyses present valuable data points that can complement standard flow cytometry data. In particular, the overlay of cell-surface proteome data with gene expression analysis presents a necessary advancement, particularly in the field of …

PMID 35344168 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 ↗

APEX Proximity Labeling of Stress Granule Proteins.

Methods in molecular biology (Clifton, N.J.) · 2022 · 2428: 381-399

Ascorbate peroxidase (APEX)-catalyzed proximity labeling has been recently established as a robust approach to uncover localized protein environments and transient protein-protein interactions occurring across mammalian cells. This molecular tool enables improved identification of individual proteins localized to and involved in …

PMID 35171492 DOI ↗

Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies.

Critical reviews in biochemistry and molecular biology · 2021 · 56(1): 31-53

Dozens of incurable neurological disorders result from expansion of short repeat sequences in both coding and non-coding regions of the transcriptome. Short repeat expansions underlie microsatellite repeat expansion (MRE) disorders including myotonic dystrophy (DM1, CUG_50-3,500 in <i>DMPK</i>; DM2, CCTG_75-11,000 in …

PMID 33172304 DOI ↗

Large-scale tethered function assays identify factors that regulate mRNA stability and translation.

Nature structural & molecular biology · 2020 · 27(10): 989-1000

The molecular functions of the majority of RNA-binding proteins (RBPs) remain unclear, highlighting a major bottleneck to a full understanding of gene expression regulation. Here, we develop a plasmid resource of 690 human RBPs that we subject to luciferase-based 3'-untranslated-region …

PMID 32807991 DOI ↗

Motoneuron expression profiling identifies an association between an axonal splice variant of HDGF-related protein 3 and peripheral myelination.

The Journal of biological chemistry · 2020 · 295(34): 12233-12246

Disorders that disrupt myelin formation during development or in adulthood, such as multiple sclerosis and peripheral neuropathies, lead to severe pathologies, illustrating myelin's crucial role in normal neural functioning. However, although our understanding of glial biology is increasing, the signals …

PMID 32647008 DOI ↗

Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.

Nature communications · 2020 · 11(1): 550

Many cellular models aimed at elucidating cancer biology do not recapitulate pathobiology including tumor heterogeneity, an inherent feature of cancer that underlies treatment resistance. Here we introduce a cancer modeling paradigm using genetically engineered human pluripotent stem cells (hiPSCs) that …

PMID 31992716 DOI ↗

Robust, Cost-Effective Profiling of RNA Binding Protein Targets with Single-end Enhanced Crosslinking and Immunoprecipitation (seCLIP).

Methods in molecular biology (Clifton, N.J.) · 2017 · 1648: 177-200

Profiling of RNA binding protein targets in vivo provides critical insights into the mechanistic roles they play in regulating RNA processing. The enhanced crosslinking and immunoprecipitation (eCLIP) methodology provides a framework for robust, reproducible identification of transcriptome-wide protein-RNA interactions, with …

PMID 28766298 DOI ↗

Erratum to: Robust, Cost-Effective Profiling of RNA Binding Protein Targets with Single-end Enhanced Crosslinking and Immunoprecipitation (seCLIP).

Methods in molecular biology (Clifton, N.J.) · 2017 · 1648: E1

PMID 29230720 DOI ↗

Short poly(A) tails are a conserved feature of highly expressed genes.

Nature structural & molecular biology · 2017 · 24(12): 1057-1063

Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not associated with translational efficiency in nonembryonic cells. To investigate whether poly(A) tail size might be coupled to …

PMID 29106412 DOI ↗