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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 ↗

Nuclear and cytoplasmic poly(A) binding proteins (PABPs) favor distinct transcripts and isoforms.

Nucleic acids research · 2022 · 50(8): 4685-4702

The poly(A)-tail appended to the 3'-end of most eukaryotic transcripts plays a key role in their stability, nuclear transport, and translation. These roles are largely mediated by Poly(A) Binding Proteins (PABPs) that coat poly(A)-tails and interact with various proteins involved …

PMID 35438785 DOI ↗

Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions.

Research square · 2022

The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral …

PMID 35313591 DOI ↗

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 ↗

Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions.

bioRxiv : the preprint server for biology · 2022

The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral …

PMID 35233578 DOI ↗

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 ↗

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 ↗

SARS-CoV-2 Distribution in Residential Housing Suggests Contact Deposition and Correlates with <i>Rothia</i> sp.

medRxiv : the preprint server for health sciences · 2021

Monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces is emerging as an important tool for identifying past exposure to individuals shedding viral RNA. Our past work has demonstrated that SARS-CoV-2 reverse transcription-quantitative PCR (RT-qPCR) signals from surfaces can …

PMID 34909793 DOI ↗

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 ↗

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 ↗

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 ↗

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 ↗

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

Cell · 2021 · 184(10): 2587-2594.e7

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in …

PMID 33861950 DOI ↗

Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS.

Molecular cell · 2021 · 81(9): 1905-1919.e12

Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to disease. At present, the full set of molecular mechanisms governing the relative …

PMID 33852893 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 ↗

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

medRxiv : the preprint server for health sciences · 2021

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated …

PMID 33564780 DOI ↗

Transcriptome-wide profiles of circular RNA and RNA-binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression.

Genome medicine · 2020 · 12(1): 112

Circular RNAs (circRNAs) are stable, often highly expressed RNA transcripts with potential to modulate other regulatory RNAs. A few circRNAs have been shown to bind RNA-binding proteins (RBPs); however, little is known about the prevalence and distribution of these interactions …

PMID 33287884 DOI ↗

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 ↗

The <i>Thermus thermophilus</i> DEAD-box protein Hera is a general RNA binding protein and plays a key role in tRNA metabolism.

RNA (New York, N.Y.) · 2020 · 26(11): 1557-1574

RNA helicases catalyze the ATP-dependent destabilization of RNA duplexes. DEAD-box helicases share a helicase core that mediates ATP binding and hydrolysis, RNA binding and unwinding. Most members of this family contain domains flanking the core that can confer RNA substrate …

PMID 32669294 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 ↗

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 ↗

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 ↗

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 ↗

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 ↗

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 ↗