366 papers
The tumour suppressor RBM5 enforces apoptotic alternative splicing by acting as a dual-action gatekeeper that physically stalls spliceosome progression while simultaneously activating the DHX15 helicase to unwind the branch helix.
This study establishes that m6A modifications regulate mRNA stability in a cell-type-specific manner in planarians, where m6A stabilizes transcripts in differentiated cells but promotes degradation in neoblasts, thereby playing a crucial role in shaping cellular identity.
Using single-nucleus RNA sequencing on iPSC-derived neuron-microglia co-cultures, this study reveals that Parkin deficiency causes distinct, cell type-specific dysregulations in dopaminergic neurons (affecting mitophagy and dopamine homeostasis) and microglia (impairing calcium homeostasis and increasing inflammatory signaling), thereby clarifying the early cellular mechanisms underlying Parkinson's disease.
This study reveals that the functional divergence between long and short isoforms of Capicua (CIC), which preferentially interact with Ataxin-1 and Ataxin-1-like respectively, underlies the distinct phenotypic outcomes of their loss and explains the regional tissue vulnerability observed in neurological diseases like Spinocerebellar ataxia type 1.
This study demonstrates that secretomes derived from both adipose- and limbal-derived mesenchymal stem cells effectively protect oxidative stress-damaged retinal pigment epithelium cells by enhancing viability, modulating inflammation and apoptosis, and inhibiting pathological angiogenesis, thereby highlighting their potential as safe, cell-free therapies for retinal degeneration.
This study presents the 2.3 Å cryo-EM structure of the CDK11-cyclin L2-SAP30BP complex to elucidate how SAP30BP stabilizes the complex and promotes assembly, identifies a C-terminal pseudo-substrate sequence involved in auto-regulation, and reveals the structural basis for the selectivity of the clinical inhibitor OTS964.
By analyzing nearly 15,000 samples across 45 human tissues, this study reveals that local tissue clocks drive widespread 24-hour gene expression rhythms, uncovering a significantly larger extent of rhythmic transcription in the brain than previously known and identifying numerous disease-associated genes with distinct diurnal phases that offer new opportunities for chronotherapeutic interventions.
This study introduces an experimental framework using deep mutational scanning and control binders to disentangle intrinsic protein-quality effects from specific protein-interaction affinities in antibody-antigen binding, revealing that current computational models largely fail to distinguish these factors and highlighting the need to account for protein quality in next-generation affinity prediction.
This study identifies copper importer CTR1 as a critical regulator of adaptive thermogenesis, demonstrating that its upregulation by cold exposure and 3-adrenergic signaling is essential for maintaining copper homeostasis, mitochondrial oxidative capacity, and lipolytic activation to sustain thermogenic responses in adipose tissues.
This study identifies a repressive upstream open reading frame (uORF) in the 5'-UTR of the epilepsy-associated gene KCNQ2 and demonstrates that disabling this uORF via mutation or adenine base editing enhances the translation of the KCNQ2 potassium channel, highlighting a novel regulatory mechanism with potential therapeutic implications.
Using nanoscale imaging, this study reveals that FUS and TAF15 functionally compensate for the loss of EWSR1 by reorganizing into a similar ribonucleoprotein network to safeguard nascent RNA levels and cellular metabolic activity, highlighting critical functional redundancy within the FET protein family.
This study reveals that Muscleblind-like (MBNL) proteins dimerize via intermolecular disulfide bonds to regulate alternative splicing and maintain the structural integrity of pathogenic RNA foci in Myotonic Dystrophy Type 1.
This study characterizes the cleavage specificity of the *E. coli* endoribonuclease YicC, demonstrating through binding and cleavage assays that its preferred substrates are small, partially structured RNAs rather than large or highly structured molecules like RyhB.
This study reveals that genome-wide DNA supercoiling in human cells is generated by transcription-driven asymmetric topological relaxation and SMC complex activity, creating a negative feedback loop where accumulated negative supercoiling represses local transcription.
This study utilized a seven-year, multi-continental sampling of wild and zoo African and Asian elephants to detect persistent low-level infections of various known and novel Elephant Endotheliotropic and Gammaherpesviruses in skin nodules, saliva, and tissues, thereby significantly expanding the genetic library for elephant virology.
This study challenges the paradigm that glycosylation is restricted to the secretory pathway by demonstrating that extended O-glycans are actively transported into the nucleus to modify RNA-binding proteins, where they play a crucial role in regulating RNA processing such as tRNA maturation.
This study identifies a conserved, transcriptionally quiescent yet functionally mature cellular state characterized by low gene complexity across diverse human tissues, which is often overlooked by standard single-cell analysis but plays a critical role in tissue maintenance and declines with aging.
This study demonstrates that the nonessential yeast protein Cwc15p tunes the spliceosome active site to ensure stability during 5' splice site cleavage and facilitate structural transitions, a function critical for splicing efficiency under nonoptimal conditions and for proofreading.
This study combines proximity labeling and novel stoichiometric structure prediction to map the composition and architecture of *Trypanosoma cruzi* bromodomain-containing CRKT and NuA4 complexes, providing a structural foundation for rational drug design against Chagas disease.
This study presents the first comprehensive body-wide expression landscape of the genetic hearing loss protein whirlin by integrating multi-omics data, revealing its broad distribution across various human tissues and cell types beyond the inner ear and retina.