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Using #SingleMolecule imaging we find that TFs:

-boost co-transcriptional #ribosomal #RNA processing!

-their binding #dynamics fundamentally differ for mRNA (transient) versus rRNA #transcription (stable)!

@biorxivpreprint.bsky.social Anastasiia Chaban @embl.org

www.biorxiv.org/content/10.6...

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Post-pandemic changes in population immunity have reduced the likelihood of emergence of zoonotic coronaviruses | Nature Communications Infections by endemic viruses, and the vaccines used to control them, often provide cross-protection against related viruses, potentially altering the transmission dynamics and likelihood of emergence of new zoonotic viruses with pandemic potential. Here, we investigate how population immunity after the COVID-19 pandemic has impacted the likelihood of emergence of a novel sarbecovirus, termed SARS-CoV-X. To this end, we combined empirical cross-neutralisation data with mathematical modelling to identify key immunological and epidemiological factors shaping sarbecovirus emergence. We show that sera from individuals with different COVID-19 immunological histories contained cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses. Simulations parameterised by these data predict that the likelihood of emergence of a novel sarbecovirus has been reduced significantly by population cross-immunity, with outcomes determined by the extent of cross-protectio

Post-COVID population immunity lowers new zoonotic coronavirus risk. Study: Cross-neutralization data + models show reduced SARS-CoV-X threat. PMID:41876522, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69988-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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NCBP1 stress signaling drives alternative S6K1 splicing inhibiting translation | Nature Chemical Biology Subcellular stress profoundly influences protein synthesis. However, both the nature of spatiotemporally restricted chemical cues and local protein responders to these cues remain elusive. Unlocking these mechanisms requires the ability to functionally map in living systems locale-specific stress responder proteins and interrogate how chemical modification of each responder impacts proteome synthesis. We resolved this problem by integrating precision localized electrophile generation and genetic code expansion tools. Upon examination of four distinct subcellular locales, only nuclear-targeted electrophile stress stalled translation. We discovered that NCBP1—a nuclear-resident protein with multifaceted roles in eukaryotic mRNA biogenesis—propagated this nuclear stress signal through a single cysteine (C436) from among its 19 conserved cysteines. This NCBP1(C436)-specific modification elicited alternative splicing of more than 250 genes. Mechanistically, global protein synthesis stall wa

NCBP₁ stress signaling alters S6K₁ splicing, hindering translation. Researchers integrated localized electrophile methods. PMID:41667655, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-025-02135-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Cardiomyocyte Cyclin-dependent kinase 9 directly binds to and phosphorylates NF-κB p65 subunit to drive cardiac inflammation and remodeling | Nature Communications Hypertensive heart failure highlights an urgent need for effective therapeutic strategies. Protein kinases regulate multiple pathways in cardiac pathophysiology and may provide promising therapeutic targets. Here, we identified a Cyclin-dependent kinase, CDK9, promoting inflammation and cardiac remodeling in terminally differentiated cardiomyocytes. Firstly, kinase enrichment analysis and experimental evidence revealed CDK9 phosphorylation at Thr-186 in both human and mouse hypertrophic heart tissues. CDK9 loss of function via T186A mutation in cardiomyocytes attenuated Ang II-induced heart remodeling and NF-κB-mediated inflammation, whereas CDK9 overactivation by T186E mutation induces. This regulatory function of CDK9 in cardiac remodeling is cell cycle-independent. Further studies demonstrate that the kinase domain of CDK9 directly binds to NF-κB P65 protein, which leads to the CDK9/P65 complex nuclear translocation, P65 phosphorylation, and transcription of inflammatory and hypertr

CDK9 phosphorylates NF-κB p65 in cardiomyocytes, fueling inflammation and remodeling in hypertensive heart failure. Potential target: Thr-186 site. PMID:41876530, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70410-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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https://www.cell.com/cell/fulltext/S0092-8674(25)01495-3 No description available

EBV alters the transcriptome and immunopeptidome in HLA-DR15+ B cells, enhancing myelin peptide presentation, potentially driving MS pathogenesis. PMID:41534530, Cell 2026, @Cell www.cell.com/cell/fulltext/S0092-8674... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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#RNA therapy 😲

scitechdaily.com/a-simple-injection-could...

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Proteomic landscape of Ewing sarcoma primary tumors and metastases | Nature Communications Ewing sarcoma (EWS), a rare pediatric bone tumor, poses unique therapeutic challenges due to its distinct microenvironment and limited molecular understanding. To gain a comprehensive molecular and functional view of the tumors in their microenvironment, we perform a deep mass spectrometry-based proteomic analysis of 170 tumor samples from 74 patients from primary, relapsed, and metastatic tumors. Analysis of more than 10,000 proteins across patients reveals insights into cancer prognosis, chemo-resistance, and progression. Our analyses suggest that ferroptosis pathways may be associated with chemotherapy response in EWS, and we delineate molecular subclasses that correlate the tumor immune landscape with DNA damage repair, ubiquitin-related proteins, and patient outcomes. Multiplexed immunofluorescence imaging indicates possible associations between neutrophils and poorer prognosis, and between macrophages/T cells and a more favorable prognosis. Altogether, this investigation provides

Ewing sarcoma proteomics: 10,000+ proteins studied in 170 tumor samples from 74 patients, offering key insights into prognosis and chemoresistance. PMID:41813675, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70449-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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The silent majority: RNAs that don’t make proteins Once considered cellular junk, non-coding RNAs are emerging as key players in everything from brain development to cancer — with much still to be discovered

“Non-coding RNAs turn out to regulate everything from embryonic development to immune responses to brain function. They help determine which genes get turned on and off, and when. They can promote cancer or suppress it.”
#Science #Scicomm #RNA #MedSky
knowablemagazine.org/content/arti...

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The silent majority: RNAs that don’t make proteins Once considered cellular junk, non-coding RNAs are emerging as key players in everything from brain development to cancer — with much still to be discovered

Dr. Jeremy Wilusz and other experts talk about non-coding RNA. #RNA

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Mast cell extracellular granules are bioactive condensates assembled by heparin and polyamine | Nature Chemical Biology Biomolecular condensates are membraneless bodies that organize biochemical reactions typically within cells. However, the roles of condensates in extracellular space—where conditions differ substantially from intracellular space—remain poorly understood. Here we report that mast cell extracellular granules (MCEGs), a stable membraneless entity, are condensates assembled through electrostatic interactions between glycosaminoglycans and polyamines. Disrupting polyamine synthesis or trafficking blocks MCEG formation and compromises the storage of proteases and cytokines. Granules reconstituted with heparin and spermine are sufficient to enrich mediators such as carboxypeptidase A3 (CPA3) and tumor necrosis factor (TNF), maintaining an elevated pH and higher concentrations of calcium and zinc compared to the extracellular milieu. This unique environment enhances CPA3 enzymatic activity. Furthermore, the granules increase TNF binding and its bioactivity toward endothelial cells. Together, w

Mast cell extracellular granules (MCEGs) are bioactive condensates formed by heparin and polyamines, crucial for immune responses. PMID:41760814, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-026-02165-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Critical Assessment of a Structure-Based Pipeline for Targeting the Long Noncoding RNA MALAT1 Long noncoding RNAs (lncRNAs) are increasingly recognized as druggable targets due to their conserved secondary/tertiary structures and regulatory roles in disease. A prototypical example is the MALAT...

🧬 lncRNA #MALAT1 as a case study to test docking on flexible #RNA targets for #drugdiscovery. HREX MD revealed two sites, whose druggability was assessed through ensemble docking of 21 diminazene derivatives and multiple scoring functions. @JCIM pubs.acs.org/doi/10.1021/...

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https://doi.org/10.1126/science.aea1820 No description available

Discover MULTI-evolve: a rapid evolution method efficiently engineering protein multimutants using AI. Transform lengthy, costly trials! PMID:41712694, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aea1820 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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RNA-specific local translation is patterned by condensates for multinucleate cell growth | Nature Cell Biology Coordination between growth and nuclear division is a common cell feature. In some syncytia, nuclei divide asynchronously throughout the cell but growth occurs only at discrete locations, raising the question how the processes are locally regulated and globally coordinated. In the syncytial fungus Ashbya gossypii, both cell cycle progression and hyphal elongation require condensates formed by the protein Whi3 in complex with distinct mRNA species. Here we show that Whi3 condensates are enriched for translation regulators and are associated with local, spatially patterned translation of specific target RNAs near nuclei and growth sites. Whi3–RNA condensates can both promote and repress mRNA translation in an RNA- and condensate size-dependent manner in vitro. Condensate interfaces are sites of translation, tunable by condensate composition, RNA valency and protein charge state in vitro. Together, these data suggest that Whi3 condensates can generate a continuum of translation states tha

In Ashbya gossypii, Whi3 protein forms RNA condensates to synchronize nuclear division and growth in multinucleate cells. PMID:41772090, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01887-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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https://doi.org/10.1001/jamadermatol.2026.0181 No description available

Discover the promise: Intralesional interleukin-2 therapy shows potential in treating high-risk or sensitive cSCC cases! 🎯📊 PMID:41848721, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0181 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Heterogeneity in lysosomal dynamics and metabolic functions along the kidney proximal tubule | Nature Communications The kidney proximal tubule is a highly specialized epithelium that transports metabolites and maintains body homeostasis. Cells lining this nephron segment are densely packed with lysosomes, but little is known about the dynamic activity of these organelles in situ. Here, using targeted sensors and live cell and intravital imaging we track acidified lysosomes along the mouse proximal tubule and uncover marked axial heterogeneity in their distribution, characteristics and organellar interactions. In the early part, cathepsin-rich lysosomes frequently contact with apical endosomes to receive and catabolize filtered plasma proteins. Conversely, in the later region, lipase-containing lysosomes traverse cells to mobilize and degrade mitochondria-associated lipid droplets and facilitate their extrusion into the tubular lumen. Acutely de-acidifying lysosomes dramatically alters their movement, causing major changes in tubular protein and lipid processing. Thus, lysosomes in proximal tubules a

Kidney proximal tubule lysosomes show dynamic, axial heterogeneity revealed via live imaging—marked differences in distribution and interactions observed.🚀 PMID:41803103, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70306-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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We are heading to #ABRF2026 in Pittsburgh, PA (March 28-31)!

Visit us at Booth #716 to explore solutions designed to support core facilities and streamline workflows for university research labs.

Let’s connect and discuss how we can help enhance your lab’s efficiency.

#NGS #DNA #RNA #RNAseq

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https://doi.org/10.1093/nar/gkag226 No description available

Genome-wide CRISPR screens reveal the EXO1-CAF-1 pathway mitigates R-loop DNA damage, critical for repair and cisplatin response. PMID:41841497, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag226 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Magnaporthe oryzae MoPh1 perceives ER stress and promotes adaptive responses via a plasma membrane-to-vacuole pathway | Nature Communications During growth and development, cells experience both internal and external stresses, which can exert harmful impacts if they are poorly managed. Endoplasmic reticulum (ER) stress is an internal stress that is induced when protein misfolding or perturbations occur at excess rates, and the conventional response pathways from the ER to the nucleus are activated to address the stress. However, the involvement of the plasma membrane (PM) system in response to this internal stress has been insufficiently investigated. Here, a PM sensor, MoPh1, was observed to perceive stress through ER-PM contact sites and target the autophagosome and vacuole, consequently stimulating the autophagy process and supporting stress relief. The PM-to-vacuole pathway mediated by MoPh1 is independent of the classical ER-to-nucleus pathway and might be highly important in both fungi and plants, as it plays a crucial role in alleviating ER stress and promoting cellular adaptation for cell survival. The unfolded prote

Discovery: Magnaporthe oryzae MoPh1 detects ER stress and boosts adaptive responses via a novel plasma membrane-vacuole route, enhancing stress management! PMID:41839901, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70610-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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https://doi.org/10.1126/science.adr4661 No description available

Study in Science: Myelin in zebrafish and rodents swells before damage but can recover via remodeling. High neuron activity worsens damage. PMID:41678629, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adr4661 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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The Approval of Redemplo for Familial Chylomicronemia Syndrome and the Many Flavors of GalNAc-Oligonucleotides - PubMed In the fourth quarter of 2025, a press release announced the approval of the eighth small interfering RNA (siRNA)-based therapeutic. Redemplo (plozasiran), developed by Arrowhead Pharmaceuticals, is…

Hot off the press from the Alterman & Khvorova labs: The Approval of Redemplo for Familial Chylomicronemia Syndrome and the Many Flavors of GalNAc-Oligonucleotides

buff.ly/chHxiUY #RNA #RNATherapeutics @UMassChan

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A bedazzled DeNovix DS-11 FX+ Spectrophotometer / Fluorometer on the Biozym Scientific booth at Analytica 2026.

A bedazzled DeNovix DS-11 FX+ Spectrophotometer / Fluorometer on the Biozym Scientific booth at Analytica 2026.

Andrew Jones and Charlie Forward smile in front of a bedazzled DeNovix DS-11 FX+ Spectrophotometer / Fluorometer on the Biozym Scientific booth at Analytica 2026.

Andrew Jones and Charlie Forward smile in front of a bedazzled DeNovix DS-11 FX+ Spectrophotometer / Fluorometer on the Biozym Scientific booth at Analytica 2026.

Attendees at Analytica 2026 chat by the Biozym Scientific booth.

Attendees at Analytica 2026 chat by the Biozym Scientific booth.

We've had a great time at #Analytica! We also had a very special DS-11 FX+ displayed on the Biozym booth to celebrate our recent Diamond Seal of Quality from SelectScience.

Enter our giveaway: go.denovix.com/sm-diamond

#Analytica2026 #LifeScience #Laboratory #DNA #RNA

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Divalent siRNA for prion disease - PubMed Prion protein (PrP) lowering is effective in animal models of prion disease and is being tested clinically in prion disease patients, but there remains a need for more potent PrP-lowering drug candidates....

Hot off the press from the RTI: Divalent siRNA for prion disease
pubmed.ncbi.nlm.nih.gov/41867745/?ut... #RNA #RNATherapeutics

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https://www.cell.com/ajhg/fulltext/S0002-9297(26)00070-4 No description available

Breakthrough in detecting de novo variants: duoNovo identifies them in 1 parent & proband; 104 trios sequenced with PacBio HiFi! #Genetics PMID:41795468, Am J Hum Genet 2026, @AJHGNews www.cell.com/ajhg/fulltext/S0002-9297... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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https://doi.org/10.1001/jamadermatol.2026.0001 No description available

Stage I-II melanoma recurrence risk linked to factors beyond ulceration & thickness. Important for patient surveillance & counseling. PMID:41779403, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0001 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Quantitative analysis of small RNA pseudouridylation reveals interplay of PUS enzymes in tRNA anticodon stem-loop | Nature Communications Pseudouridine (Ψ) is an abundant modification in small RNA catalyzed by multiple pseudouridine synthases (PUSs). However, the substrate specificity of human PUSs remains elusive. Here, we adopted PRAISE, a quantitative Ψ detection method, to profile pseudouridylation in small RNA, including cytosolic and mitochondrial tRNAs, snRNA, and snoRNA. We found that snoRNA pseudouridylation is mediated not only by RNA-guided DKC1, but also by the stand-alone enzyme PUS7 at a specific site. Interestingly, several PUS enzymes, including PUS1, RPUSD1, and PUS7, which install nearby Ψ sites within tRNA anticodon stem-loop, can influence pseudouridylation catalyzed by other PUSs, revealing an unrecognized interplay during Ψ formation. For the three RluA family enzymes, RPUSD1 catalyzes the canonical Ψ30 in tRNA-Ile and Ψ72 in tRNA-Arg isoacceptors. RPUSD2 pseudouridylates Ψ31 of mt-tRNALeu(CUN), Ψ32 of mt-tRNAPro and mt-tRNACys, whereas RPUSD3 lacks tRNA activity. Together, our quantitative Ψ profil

Discover how pseudouridine (Ψ) tweaks small RNA! A study using PRAISE shows snoRNA gets pseudouridylation via DKC1 and PUS7, revealing PUS enzyme teamwork. PMID:41698914, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69177-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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A red/blue optoswitch for temporal control of chloroplast transcription and biogenesis in Arabidopsis | Nature Communications Photosynthesis genes in plant chloroplasts are transcribed by the plastid-encoded RNA polymerase called PEP. Consequently, PEP-deficient mutants cannot generate a photosynthetic apparatus and develop non-viable albino seedlings. Inducible complementation of such mutants thus could provide interesting insights in PEP action and chloroplast biogenesis. Here we show the effects of photo-inducible complementation in the albino Arabidopsis mutant pap7-1 using a red/blue optoswitch with monochromatic LEDs. Expression of a blue-light-induced PAP7 construct that is silent under red light reconstitutes PEP at any time point of pap7-1 development resulting in proper chloroplast biogenesis that rescues the non-viable mutant. Induction of chloroplast biogenesis, however, can only occur in very young leaf tissues indicating the existence of a cell-autonomous, biogenic coupling between cell and organelle development. We further uncover that initial PEP formation and function is independent of photos

Revealed: Red/blue optoswitch rescues albino mutant Arabidopsis pap7-1 by regulating chloroplast transcription. Discoveries in PEP action and biogenesis! PMID:41720790, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69626-3 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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https://doi.org/10.1001/jamadermatol.2025.4860 No description available

Case of #MulticentricReticulohistiocytosis: extensive erythema (face, chest, back) & swollen hands with papules/nodules observed. PMID:41637085, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2025.4860 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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https://doi.org/10.1056/NEJMoa2508515 No description available

Phase 3 trial: Tenecteplase 0.25 mg/kg vs placebo in central retinal artery occlusion (within 4.5h onset). Could change vision loss treatment! PMID:41604638, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMoa2508515 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Post-Transcriptional Size-Dependent Expression of the Fission Yeast Cdc13 Cyclin The major fission yeast cyclin, Cdc13, has been shown to increase in concentration in correlation with cell size, and has been proposed to thereby regulate cell size at division. However, the mechanism...

🧬 New BioRxiv preprint from the RTI: Post-Transcriptional Size-Dependent Expression of the Fission Yeast Cdc13 Cyclin www.biorxiv.org/content/10.1... #RNA #RNATherapeutics @umasschan.bsky.social

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Exploring Secondary Structure Predictions for RNA-Targeted Drug Discovery: Power and Challenges RNAs are increasingly recognized as promising drug targets, as both coding and noncoding RNAs act as key regulators in disease-related biological processes. However, a significant gap persists between...

New paper published! @bussigio.bsky.social contributed to a work led by Zhengyue Zhang @astrazeneca.com where #RNA secondary-structure prediction methods were benchmarked in the context of #RNA-targeted #drugdiscovery. doi.org/10.1021/acs....

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