Search publications
88 results for “gene regulation”
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Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death.
Nature communications · 2023 · 14(1): 551
Regulation of RNA processing contributes profoundly to tissue development and physiology. Here, we report that serine-arginine-rich splicing factor 1 (SRSF1) is essential for hepatocyte function and survival. Although SRSF1 is mainly known for its many roles in mRNA metabolism, it …
PMID 36759613 DOI ↗
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RNA binding protein DDX5 restricts RORγt<sup>+</sup> T<sub>reg</sub> suppressor function to promote intestine inflammation.
Science advances · 2023 · 9(5): eadd6165
Retinoid-related orphan receptor (RAR) gamma (RORγt)-expressing regulatory T cells (RORγt<sup>+</sup> T<sub>regs</sub>) play pivotal roles in preventing T cell hyperactivation and maintaining tissue homeostasis, in part by secreting the anti-inflammation cytokine interleukin-10 (IL-10). Here, we report that hypoxia-induced factor 1α (HIF1α) …
PMID 36724232 DOI ↗
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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 ↗
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RBP Image Database: A resource for the systematic characterization of the subcellular distribution properties of human RNA binding proteins.
Nucleic acids research · 2023 · 51(D1): D1549-D1557
RNA binding proteins (RBPs) are central regulators of gene expression implicated in all facets of RNA metabolism. As such, they play key roles in cellular physiology and disease etiology. Since different steps of post-transcriptional gene expression tend to occur in …
PMID 36321651 DOI ↗
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RNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine.
Gut · 2022 · 71(9): 1790-1802
Tuft cells residing in the intestinal epithelium have diverse functions. In the small intestine, they provide protection against inflammation, combat against helminth and protist infections, and serve as entry portals for enteroviruses. In the colon, they had been implicated in …
PMID 34853057 DOI ↗
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The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression.
The Journal of experimental medicine · 2022 · 219(6)
During an immune response to microbial infection, CD8+ T cells give rise to short-lived effector cells and memory cells that provide sustained protection. Although the transcriptional programs regulating CD8+ T cell differentiation have been extensively characterized, the role of long …
PMID 35593887 DOI ↗
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Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML.
Cell reports · 2022 · 38(10): 110481
Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA and protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this …
PMID 35263585 DOI ↗
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Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis.
Cellular and molecular life sciences : CMLS · 2022 · 79(3): 147
In addition to genomic alterations, aberrant changes in post-transcriptional regulation can modify gene function and drive cancer development. RNA-binding proteins (RBPs) are a large class of post-transcriptional regulators that have been increasingly implicated in carcinogenesis. By integrating multi-omics data, we …
PMID 35195778 DOI ↗
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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 ↗
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Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies.
Nature communications · 2021 · 12(1): 6324
Mutations in the cardiac splicing factor RBM20 lead to malignant dilated cardiomyopathy (DCM). To understand the mechanism of RBM20-associated DCM, we engineered isogenic iPSCs with DCM-associated missense mutations in RBM20 as well as RBM20 knockout (KO) iPSCs. iPSC-derived engineered heart …
PMID 34732726 DOI ↗
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Non-microRNA binding competitively inhibits LIN28 regulation.
Cell reports · 2021 · 36(6): 109517
RNA binding protein (RBP) expression is finite. For RBPs that are vastly outnumbered by their potential target sites, a simple competition for binding can set the magnitude of post-transcriptional control. Here, we show that LIN28, best known for its direct …
PMID 34380031 DOI ↗
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Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer.
Molecular cell · 2021 · 81(15): 3048-3064.e9
RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression, and aberrant RBP-RNA interactions can promote cancer progression. Here, we interrogate the function of RBPs in cancer using pooled CRISPR-Cas9 screening and identify 57 RBP candidates with distinct roles in …
PMID 34216543 DOI ↗
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Robust single-cell discovery of RNA targets of RNA-binding proteins and ribosomes.
Nature methods · 2021 · 18(5): 507-519
RNA-binding proteins (RBPs) are critical regulators of gene expression and RNA processing that are required for gene function. Yet the dynamics of RBP regulation in single cells is unknown. To address this gap in understanding, we developed STAMP (Surveying Targets …
PMID 33963355 DOI ↗
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Footprinting SHAPE-eCLIP Reveals Transcriptome-wide Hydrogen Bonds at RNA-Protein Interfaces.
Molecular cell · 2020 · 80(5): 903-914.e8
Discovering the interaction mechanism and location of RNA-binding proteins (RBPs) on RNA is critical for understanding gene expression regulation. Here, we apply selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) on in vivo transcripts compared to protein-absent transcripts in four …
PMID 33242392 DOI ↗
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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 ↗
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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 ↗
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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 ↗
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Context-dependent functional compensation between Ythdf m<sup>6</sup>A reader proteins.
Genes & development · 2020 · 34(19-20): 1373-1391
The N6-methyladenosine (m<sup>6</sup>A) 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 ↗
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Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action.
Proceedings of the National Academy of Sciences of the United States of America · 2020 · 117(36): 22204-22213
The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a transcriptional coactivator that controls expression of metabolic/energetic genes, programming cellular responses to nutrient and environmental adaptations such as fasting, cold, or exercise. Unlike other coactivators, PGC-1α contains protein domains involved …
PMID 32848060 DOI ↗
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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 ↗
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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 ↗
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A large-scale binding and functional map of human RNA-binding proteins.
Nature · 2020 · 583(7818): 711-719
Many proteins regulate the expression of genes by binding to specific regions encoded in the genome<sup>1</sup>. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part …
PMID 32728246 DOI ↗
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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 ↗
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Heterogenous Populations of Tissue-Resident CD8<sup>+</sup> T Cells Are Generated in Response to Infection and Malignancy.
Immunity · 2020 · 52(5): 808-824.e7
Tissue-resident memory CD8<sup>+</sup> T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8<sup>+</sup> T cells, including a Blimp1<sup>hi</sup>Id3<sup>lo</sup> tissue-resident effector cell population …
PMID 32433949 DOI ↗
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Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription.
Cell · 2019 · 178(1): 107-121.e18
Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA-binding proteins (RBPs). Although multiple RBPs have been implicated in transcription control, it has remained unclear how extensively RBPs directly act on …
PMID 31251911 DOI ↗
Datasets 14
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [PAS-seq]
Homo sapiens · Illumina
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [RNA-Seq]
Homo sapiens · Illumina
Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [eCLIP]
Homo sapiens · Illumina
Loss of canonical splicing factor SRSF1 in hepatocytes results in acute liver injury and regeneration
Mus musculus · GPL21103
Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling
Homo sapiens · GPL24676
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
Homo sapiens · GPL30173
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
Homo sapiens · GPL24676
Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [RNA-seq]
Homo sapiens · GPL24676
Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [RBNS]
synthetic construct · GPL34014
Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [SLAM-Seq]
Homo sapiens · GPL24676
Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [Cut&Run]
Homo sapiens · GPL24676
Skipper analysis of RNA-protein interactions highlights depletion of genetic variation in translation factor binding sites
Homo sapiens · GPL24676
Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [eCLIP]
Homo sapiens · GPL24676
Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [Ribo-STAMP cell lines]
Homo sapiens · GPL24676
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