Search publications

Single-cell and isoform-specific translational profiling of the mouse brain.

Nature · 2026

The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation^1-11. Among these, alternative splicing has been shown to drive cell-type specificity and, when disrupted, is strongly linked to neurological disorders^12-17. However, genome-wide measurements of mRNA translation with isoform …

PMID 41708856 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 ↗

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 ↗

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 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 ↗

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 ↗

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 ↗

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 ↗

Engineered U1 snRNAs to modulate alternatively spliced exons.

Methods (San Diego, Calif.) · 2022 · 205: 140-148

Alternative splicing accounts for a considerable portion of transcriptomic diversity, as most protein-coding genes are spliced into multiple mRNA isoforms. However, errors in splicing patterns can give rise to mis-splicing with pathological consequences, such as the congenital diseases familial dysautonomia, …

PMID 35764245 DOI ↗

Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms.

Cancer discovery · 2022 · 12(3): 836-855

Mutations in splicing factors (SF) are the predominant class of mutations in myelodysplastic syndrome (MDS), but convergent downstream disease drivers remain elusive. To identify common direct targets of missplicing by mutant U2AF1 and SRSF2, we performed RNA sequencing and enhanced …

PMID 34620690 DOI ↗

Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.

Molecular cell · 2022 · 82(3): 645-659.e9

Pseudouridine is a modified nucleotide that is prevalent in human mRNAs and is dynamically regulated. Here, we investigate when in their life cycle mRNAs become pseudouridylated to illuminate the potential regulatory functions of endogenous mRNA pseudouridylation. Using single-nucleotide resolution pseudouridine …

PMID 35051350 DOI ↗

Erratum: A role for alternative splicing in circadian control of exocytosis and glucose homeostasis.

Genes & development · 2021 · 35(5-6): 425

PMID 33649163 DOI ↗

A role for alternative splicing in circadian control of exocytosis and glucose homeostasis.

Genes & development · 2020 · 34(15-16): 1089-1105

The circadian clock is encoded by a negative transcriptional feedback loop that coordinates physiology and behavior through molecular programs that remain incompletely understood. Here, we reveal rhythmic genome-wide alternative splicing (AS) of pre-mRNAs encoding regulators of peptidergic secretion within pancreatic …

PMID 32616519 DOI ↗

RBP-Maps enables robust generation of splicing regulatory maps.

RNA (New York, N.Y.) · 2019 · 25(2): 193-204

Alternative splicing of pre-messenger RNA transcripts enables the generation of multiple protein isoforms from the same gene locus, providing a major source of protein diversity in mammalian genomes. RNA binding proteins (RBPs) bind to RNA to control splice site choice …

PMID 30413564 DOI ↗

Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation.

Molecular cell · 2017 · 67(1): 148-161.e5

Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational …

PMID 28673540 DOI ↗

Experimental and Computational Considerations in the Study of RNA-Binding Protein-RNA Interactions.

Advances in experimental medicine and biology · 2016 · 907: 1-28

After an RNA is transcribed, it undergoes a variety of processing steps that can change the encoded protein sequence (through alternative splicing and RNA editing), regulate the stability of the RNA, and control subcellular localization, timing, and rate of translation. …

PMID 27256380 DOI ↗

RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

Nature structural & molecular biology · 2016 · 23(12): 1101-1110

Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions …

PMID 27775709 DOI ↗

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

Neuron · 2016 · 92(4): 780-795

HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …

PMID 27773581 DOI ↗

The Calcineurin Variant CnAβ1 Controls Mouse Embryonic Stem Cell Differentiation by Directing mTORC2 Membrane Localization and Activation.

Cell chemical biology · 2016 · 23(11): 1372-1382

Embryonic stem cells (ESC) have the potential to generate all the cell lineages that form the body. However, the molecular mechanisms underlying ESC differentiation and especially the role of alternative splicing in this process remain poorly understood. Here, we show …

PMID 27746127 DOI ↗

Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.

Nature communications · 2016 · 7: 12143

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs …

PMID 27378374 DOI ↗

Dysregulation of RBFOX2 Is an Early Event in Cardiac Pathogenesis of Diabetes.

Cell reports · 2016 · 15(10): 2200-2213

Alternative splicing (AS) defects that adversely affect gene expression and function have been identified in diabetic hearts; however, the mechanisms responsible are largely unknown. Here, we show that the RNA-binding protein RBFOX2 contributes to transcriptome changes under diabetic conditions. RBFOX2 …

PMID 27239029 DOI ↗

Nxf1 natural variant E610G is a semi-dominant suppressor of IAP-induced RNA processing defects.

PLoS genetics · 2015 · 11(4): e1005123

Endogenous retroviruses and retrotransposons contribute functional genetic variation in animal genomes. In mice, Intracisternal A Particles (IAPs) are a frequent source of both new mutations and polymorphism across laboratory strains. Intronic IAPs can induce alternative RNA processing choices, including alternative …

PMID 25835743 DOI ↗

A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

PloS one · 2014 · 9(12): e113258

The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe …

PMID 25474699 DOI ↗

Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges.

Nature structural & molecular biology · 2013 · 20(12): 1434-42

Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an …

PMID 24213538 DOI ↗