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Zfp697/ZNF697 is an RNA-binding protein that modulates TGF-β1 signaling and hepatic inflammation in liver disease.

Molecular metabolism · 2026 : 102457

Liver diseases driven by metabolic dysfunction, inflammation, and fibrosis such as metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH), and acute liver injury represent a growing global health burden. The zinc finger protein Zfp697 (ZNF697 in humans) …

PMID 42875003 DOI ↗

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 ↗

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 ↗

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 ↗

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 ↗

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

Nature · 2025 · 639(8054): 483-492

Tissue-resident memory CD8 T (T_RM) cells provide protection from infection at barrier sites. In the small intestine, T_RM cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential¹. …

PMID 39843748 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 ↗

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 ↗

Epistatic interactions between NMD and TRP53 control progenitor cell maintenance and brain size.

Neuron · 2024 · 112(13): 2157-2176.e12

Mutations in human nonsense-mediated mRNA decay (NMD) factors are enriched in neurodevelopmental disorders. We show that deletion of key NMD factor Upf2 in mouse embryonic neural progenitor cells causes perinatal microcephaly but deletion in immature neurons does not, indicating NMD's …

PMID 38697111 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 ↗

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 ↗

The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.

Cellular and molecular gastroenterology and hepatology · 2022 · 14(1): 35-53

Hyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy. Pre- and …

PMID 35378331 DOI ↗

Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma.

Nature communications · 2022 · 13(1): 7506

Pediatric medulloblastoma (MB) is the most common solid malignant brain neoplasm, with Group 3 (G3) MB representing the most aggressive subgroup. MYC amplification is an independent poor prognostic factor in G3 MB, however, therapeutic targeting of the MYC pathway remains …

PMID 36473869 DOI ↗

Author Correction: Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Nature · 2022 · 605(7909): E3

PMID 35474001 DOI ↗

The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1.

Nature biomedical engineering · 2021 · 5(2): 157-168

Myotonic dystrophy type I (DM1) is a multisystemic autosomal-dominant inherited human disorder that is caused by CTG microsatellite repeat expansions (MREs) in the 3' untranslated region of DMPK. Toxic RNAs expressed from such repetitive sequences can be eliminated using CRISPR-mediated …

PMID 32929188 DOI ↗

Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program.

Molecular cell · 2020 · 80(3): 452-469.e9

Although TP53 is the most commonly mutated gene in human cancers, the p53-dependent transcriptional programs mediating tumor suppression remain incompletely understood. Here, to uncover critical components downstream of p53 in tumor suppression, we perform unbiased RNAi and CRISPR-Cas9-based genetic screens …

PMID 33157015 DOI ↗

AMPK regulation of Raptor and TSC2 mediate metformin effects on transcriptional control of anabolism and inflammation.

Genes & development · 2020 · 34(19-20): 1330-1344

Despite being the frontline therapy for type 2 diabetes, the mechanisms of action of the biguanide drug metformin are still being discovered. In particular, the detailed molecular interplays between the AMPK and the mTORC1 pathway in the hepatic benefits of …

PMID 32912901 DOI ↗

Context-dependent functional compensation between Ythdf m⁶A reader proteins.

Genes & development · 2020 · 34(19-20): 1373-1391

The N6-methyladenosine (m⁶A) modification is the most prevalent post-transcriptional mRNA modification, regulating mRNA decay and splicing. It plays a major role during normal development, differentiation, and disease progression. The modification is regulated by a set of writer, eraser, and reader …

PMID 32943573 DOI ↗

Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Nature · 2020 · 583(7818): 699-710

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded …

PMID 32728249 DOI ↗

Suppression of Endothelial AGO1 Promotes Adipose Tissue Browning and Improves Metabolic Dysfunction.

Circulation · 2020 · 142(4): 365-379

Metabolic disorders such as obesity and diabetes mellitus can cause dysfunction of endothelial cells (ECs) and vascular rarefaction in adipose tissues. However, the modulatory role of ECs in adipose tissue function is not fully understood. Other than vascular endothelial growth …

PMID 32393053 DOI ↗

An in vivo genome-wide CRISPR screen identifies the RNA-binding protein Staufen2 as a key regulator of myeloid leukemia.

Nature cancer · 2020 · 1(4): 410-422

Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, …

PMID 34109316 DOI ↗

The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis.

Cell stem cell · 2019 · 25(5): 622-638.e13

Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells …

PMID 31588046 DOI ↗

Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9.

Nucleic acids research · 2018 · 46(14): 7323-7338

Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of …

PMID 29733375 DOI ↗