376 papers
This study reveals that the HMD domain of the PAF1C subunit Prf1 activates the S. pombe HULC complex for H2B ubiquitination by binding to a specific region on Shf1 to reposition the RING domains into a catalytically competent configuration, thereby elucidating the molecular mechanism by which PAF1C primes the Rad6-Bre1 E3 ligase for transcription-coupled histone modification.
This study demonstrates that 23S rRNA modifications near the peptidyl transferase center are essential for stabilizing the ribosome's native structure, thereby preventing nonfunctional alternative conformations and ensuring optimal catalytic efficiency and thermal stability during translation.
The paper introduces FlashPPI, a contrastive learning framework that leverages genomic language models to enable linear-time, proteome-scale prediction of microbial protein-protein interactions with accuracy comparable to structure-folding models but at a fraction of the computational cost.
This study utilizes near single-cell spatial transcriptomics to reveal that anatomically distinct neuroendocrine tumors share a conserved stromal architecture characterized by two dominant, spatially segregated cancer-associated fibroblast states: myofibroblastic cells enriched in collagen-dense regions and complement-secreting cells localized at tumor-stroma interfaces.
This study reveals a novel RNA-guided transcription mechanism in which exapted CRISPR-Cas12f homologs recruit sigma E factors to programmatically activate gene expression without canonical promoter motifs, effectively mimicking human-engineered CRISPR activation systems.
This study reveals that whiteflies and planthoppers have independently evolved distinct salivary effectors (BtRDP and NlSP104) to suppress plant immunity by targeting and promoting the degradation of the conserved receptor-like protein RLP4, thereby illustrating a convergent evolutionary strategy for herbivorous insects to counteract host defenses.
By integrating full-length single-nucleus transcriptomics with gold-standard metabolic clamps, this study redefines skeletal muscle insulin resistance as a nucleus-resolved multicellular process, identifying specific myonuclear populations and molecular regulators like ZIP14 and EGF signaling that drive metabolic dysfunction.
This study reveals that the phosphatases Ppz1 and Ppz2 induce autophagy in yeast by dephosphorylating and suppressing potassium transporters Trk1 and Trk2, thereby lowering intracellular potassium levels to a critical threshold required for the process.
This study reveals that the direct physical interaction between OTULIN and LUBAC serves as a critical regulatory brake that restrains LUBAC's enzymatic activity and Met1-Ub accumulation to prevent TNF-driven immunopathology and maintain tissue integrity during acute immune responses.
This study introduces an automated, force-adjustable *Drosophila* model of repetitive traumatic brain injury that reveals sex-specific differences in locomotor vulnerability and survival, alongside shared cognitive deficits, progressive neurodegeneration, and distinct proteomic disruptions involving mitochondrial and oxidative stress pathways.
This study presents the first fully phased, telomere-to-telomere reference genome assemblies for a Thoroughbred horse and a donkey, derived from a mule offspring, which reveal unprecedented insights into equid centromere plasticity, the uncoupling of satellite DNA from centromeric function, and the accelerated karyotypic evolution of the Equidae family.
This study presents the development and validation of three Cre-dependent CRISPR-based mouse lines that enable inducible, locus-specific DNA methylation editing in vivo, successfully demonstrating causal links between methylation and gene expression at specific genomic loci in both ex vivo myeloid cells and in vivo neurons.
This study demonstrates that in *Leishmania major*, the hyper-modified DNA base J is essential for preventing RNA polymerase II readthrough transcription at telomeres, thereby regulating TERRA levels to maintain telomere integrity, ensure cell viability, and control the differentiation of promastigotes into the infectious metacyclic stage.
This study identifies the pathological co-activation of developmental Notch and WNT signaling pathways as a unique driver of myocardial stiffening and dysfunction in pediatric dilated cardiomyopathy, demonstrating that inhibiting this axis improves cardiac function and supporting the need for age-specific therapeutic strategies distinct from adult heart failure treatments.
This study demonstrates that IL1R1 antagonists actively block inflammatory signaling not by failing to stabilize an active state, but by dynamically increasing flexibility in the distal D3 domain to allosterically prevent co-receptor recruitment, thereby revealing receptor dynamics as a critical determinant of signaling control.
This study reveals that HIF-1α coordinates adrenal steroidogenesis under hypoxia by directly regulating steroidogenic genes and selectively modulating the expression of miRNA biogenesis machinery to shape post-transcriptional control.
This study characterizes the genetic diversity and recombination patterns of the ORF7 gene in ten PRRSV-2 strains from Lima, Peru, revealing the co-circulation of NADC34-like and VR2332-like lineages, significant amino acid substitutions in antigenic regions, and inter-lineage recombination events that underscore the need for continuous molecular surveillance to support effective disease control.
This study establishes a longitudinal in vivo human wound healing model revealing that vascular smooth muscle cells, through TIMP1-mediated extracellular matrix remodeling, are critical drivers of effective tissue repair, while their dysfunction underlies the impaired healing observed in diabetic foot ulcers.
This study reveals that the histone chaperone FACT is essential for mammalian replication and transcription by dynamically disassembling and reassembling nucleosomes to maintain chromatin structure and prevent genome aggregation.
This study reveals that a subset of miRNAs, particularly miR-21, localizes to the nucleus in anthropoid primates to form RNA-DNA triplexes with Argonaute 2, representing an evolutionarily recent mechanism for chromatin-based gene regulation.