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Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted.

bioRxiv : the preprint server for biology · 2024

Tissue-resident memory CD8 T cells (T_RM) kill infected cells and recruit additional immune cells to limit pathogen invasion at barrier sites. Small intestinal (SI) T_RM cells consist of distinct subpopulations with higher expression of effector molecules or greater memory potential. …

PMID 38585842 DOI ↗

Junior scientists spotlight social bonds in seminars for diversity, equity, and inclusion in STEM.

PloS one · 2023 · 18(11): e0293322

Disparities for women and minorities in science, technology, engineering, and math (STEM) careers have continued even amidst mounting evidence for the superior performance of diverse workforces. In response, we launched the Diversity and Science Lecture series, a cross-institutional platform where …

PMID 37917746 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 ↗

A phage nucleus-associated RNA-binding protein is required for jumbo phage infection.

bioRxiv : the preprint server for biology · 2023

Large-genome bacteriophages (jumbo phages) of the <i>Chimalliviridae</i> family assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and CRISPR/Cas nucleases. While the nuclear shell provides broad protection against host nucleases, …

PMID 37790334 DOI ↗

Remodeling oncogenic transcriptomes by small molecules targeting NONO.

Nature chemical biology · 2023 · 19(7): 825-836

Much of the human proteome is involved in mRNA homeostasis, but most RNA-binding proteins lack chemical probes. Here we identify electrophilic small molecules that rapidly and stereoselectively decrease the expression of transcripts encoding the androgen receptor and its splice variants …

PMID 36864190 DOI ↗

Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling.

Nucleic acids research · 2023 · 51(12): 6461-6478

In light of the numerous studies identifying post-transcriptional regulators on the surface of the endoplasmic reticulum (ER), we asked whether there are factors that regulate compartment specific mRNA translation in human cells. Using a proteomic survey of spatially regulated polysome …

PMID 37224531 DOI ↗

Skipper analysis of eCLIP datasets enables sensitive detection of constrained translation factor binding sites.

Cell genomics · 2023 · 3(6): 100317

Technology for crosslinking and immunoprecipitation (CLIP) followed by sequencing (CLIP-seq) has identified the transcriptomic targets of hundreds of RNA-binding proteins in cells. To increase the power of existing and future CLIP-seq datasets, we introduce Skipper, an end-to-end workflow that converts …

PMID 37388912 DOI ↗

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 ↗

RNA binding protein DDX5 restricts RORγt⁺ T_reg suppressor function to promote intestine inflammation.

Science advances · 2023 · 9(5): eadd6165

Retinoid-related orphan receptor (RAR) gamma (RORγt)-expressing regulatory T cells (RORγt⁺ T_regs) 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 ↗

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 ↗

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

Nature communications · 2023 · 14(1): 136

PMID 36627300 DOI ↗

Small intestine and colon tissue-resident memory CD8⁺ T cells exhibit molecular heterogeneity and differential dependence on Eomes.

Immunity · 2023 · 56(1): 207-223.e8

Tissue-resident memory CD8⁺ T (T_RM) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. T_RM cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments …

PMID 36580919 DOI ↗

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 ↗

Examination of the Cell Cycle Dependence of Cytosine and Adenine Base Editors.

Frontiers in genome editing · 2022 · 4: 923718

Base editors (BEs) are genome editing agents that install point mutations with high efficiency and specificity. Due to their reliance on uracil and inosine DNA damage intermediates (rather than double-strand DNA breaks, or DSBs), it has been hypothesized that BEs …

PMID 35910415 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 ↗

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 ↗

Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampus.

Neurobiology of disease · 2022 · 172: 105834

Synapse dysfunction and loss are central features of neurodegenerative diseases, caused in part by the accumulation of protein oligomers. Amyloid-β, tau, prion, and α-synuclein oligomers bind to the cellular prion protein (PrP^C), resulting in the activation of macromolecular complexes and …

PMID 35905927 DOI ↗

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 ↗

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 ↗

The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors.

Nature communications · 2022 · 13(1): 3833

Chemo-resistance in acute myeloid leukemia (AML) patients is driven by leukemic stem cells (LSCs) resulting in high rates of relapse and low overall survival. Here, we demonstrate that upregulation of the splicing factor, RBM17 preferentially marks and sustains LSCs and …

PMID 35781533 DOI ↗

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

mSystems · 2022 · 7(3): e0141121

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 demonstrated that SARS-CoV-2 reverse transcription-quantitative PCR (RT-qPCR) signals from surfaces can identify …

PMID 35575492 DOI ↗

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 ↗