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Research Articles
FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stressThis work shows that the ALS-associated protein FUS is a component of the cellular response to transcriptional stress induced by topoisomerase I–induced DNA breakage, thereby accumulating at sites of nucleolar rRNA synthesis.
Worldwide genetic variation of the IGHV and TRBV immune receptor gene families in humansThis article presents a comprehensive study of the IGHV and TRBV gene families in a globally diverse sample of humans and shows that the two gene families exhibit starkly different patterns of variation.
Assessment and site-specific manipulation of DNA (hydroxy-)methylation during mouse corticogenesisThis work describes the dynamics of DNA modifications in specific cell types of the developing mammalian cortex. By providing a new method to manipulate this process in vivo, it is shown how this process can influence brain formation.
Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturationMaternal gestational circulating microRNAs, predictive of adverse infant outcomes, including growth deficits, following prenatal alcohol exposure, contribute to placental pathology by impairing the EMT pathway in trophoblasts.
The small and large ribosomal subunits depend on each other for stability and accumulationStopping 60S assembly blocks accumulation of 40S by post-assembly turnover, whereas inhibiting 40S assembly allows 60S assembly but results in fragmentation of 25S rRNA.
Innate extracellular vesicles from melanoma patients suppress β-catenin in tumor cells by miRNA-34aOperated cancer patients develop elevated levels of extracellular vesicles (EVs) in their blood stream, suppressing cancer cells through miRNA-34a.
PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changesThis work demonstrates that pathogenic variants in PISD cause mitochondrial disease and suggests a novel mechanistic link whereby impaired lipid content in the inner mitochondrial membrane alters the activity of inner mitochondrial membrane proteases.
Expanding the repertoire of glucocorticoid receptor target genes by engineering genomic response elementsThis study shows that addition of a single transcription factor binding site can be sufficient to convert a gene into a glucocorticoid receptor target.
Structural basis of guanine nucleotide exchange for Rab11 by SH3BP5The structure of the SH3BP5–Rab11a complex and structure-based mutational analyses reveal structural basis of nucleotide exchange for Rab11 by its specific guanine nucleotide exchange factor.
Dependence on Myb expression is attenuated in myeloid leukaemia with N-terminal CEBPA mutationsWe show that for acute myeloid leukaemias with CEBPA mutations, the dependency of leukaemia growth and differentiation on the Myb transcription factor is related to the combination of N- and C-terminal mutations involved and how this affects overall gene expression.
Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunitThe subunit p12 of human DNA polymerase delta (hPolδ) can dimerize, facilitating its interaction with PCNA and suggesting that hPolδ exists in a pentameric form in the cell.
Sex-regulated gene dosage effect of PPARα on synaptic plasticityDifferences in PPARα expression between males and females affect the regulation of GluA1 expression and synaptic plasticity in mice.
Functional inhibition of acid sphingomyelinase disrupts infection by intracellular bacterial pathogensMany intracellular pathogens hijack cholesterol. Inhibiting acid sphingomyelinase alters cholesterol traffic to target different intracellular bacteria, signifying a host-directed approach for treating infectious disease.
Drug screening with human SMN2 reporter identifies SMN protein stabilizers to correct SMA pathologyThis study has established a versatile human SMN2 reporter line for drug screening and identified a novel strategy of targeting cysteine proteases for rescuing SMA pathological phenotypes.
let-7 coordinates the transition to adulthood through a single primary and four secondary targetsAlthough miRNAs may act through regulation of numerous targets, this study shows that the Caenorhabditis elegans let-7 miRNA promotes the juvenile-to-adult transition through repression of LIN41 alone, thereby activating four LIN41 targets that function in pairs to execute distinct developmental functions.
Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesisPer-cell quantification of mTORC1 signaling activity in neural stem/progenitor cells reveals differential signaling, proliferative, and tumor-forming capability between dorsal and ventral cells within a single niche.
A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesisOur study highlights a dual role for SAMHD1 in regulating hepatitis B virus cccDNA levels and reverse transcriptase–dependent particle genesis.
Epidermal development requires ninein for spindle orientation and cortical microtubule organizationIn the epidermis, ninein affects spindle orientation of progenitor cells, as well as cortical microtubule organization, desmosome assembly, and lamellar body secretion in differentiating cells.
The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical mannerPI3K and p38 act in a hierarchical manner to enhance mTORC1 activity and stress granule formation; although PI3K is the main driver, the impact of p38 gets apparent as PI3K activity declines.
BZLF1 interacts with chromatin remodelers promoting escape from latent infections with EBVHow herpesviruses escape from their latent states is enigmatic, but BZLF1, an important transcription factor of EBV, recruits cellular chromatin remodelers to viral DNA to overcome its epigenetic repression and initiate viral transcription.
Human NK cell development in hIL-7 and hIL-15 knockin NOD/SCID/IL2rgKO miceA new humanized mouse expressing human IL-7 and IL-15 facilitates development and maturation of human NK cells and can be useful as a preclinical in vivo model for testing new treatment modalities.
Intra-individual methylomics detects the impact of early-life adversityThis study shows that methylation profile changes across time in the same individual distinguish a stressful experience from typical infancy, providing a potential predictive marker of vulnerability to disease.
ROS amplification drives mouse spermatogonial stem cell self-renewalAlthough reactive oxygen species (ROS) are required for spermatogonial stem cell (SSC) self-renewal, the mechanism has remained unknown. We show that SSC self-renewal signals activate MAPK14/MAPK7 pathway to induce nuclear translocation of BCL6B and activation of NOX1.
Constitutive STAT5 activation regulates Paneth and Paneth-like cells to control Clostridium difficile colitisSTAT5 controls the intestinal epithelial stem cell niche by regulating Wnt/β-catenin signaling, and lack of active pYSTAT5 induces Clostridium difficile infection. STAT5 may be a transcription factor that restricts niche cell differentiation.
m6A-mRNA methylation regulates cardiac gene expression and cellular growthThis study provides evidence that m6A methylation is dynamically regulated during human and murine cardiac disease and highlights an important role of the m6A methylase Mettl3 in regulating cardiac growth by gene expression control.
CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growthInhibition of the CXXC5–DVL interaction is a potential therapeutic strategy for height enhancement of children with growth retardation.
Mitotic replisome disassembly depends on TRAIP ubiquitin ligase activityAnalysis of the mitotic replisome disassembly pathway in X. laevis egg extract shows that any replisomes retained on chromatin past S-phase are unloaded through formation of K6- and K63-linked ubiquitin chains on Mcm7 by TRAIP ubiquitin ligase and p97/VCP activity.
A network of human functional gene interactions from knockout fitness screens in cancer cellsThe function of human genes can be strongly inferred from their knockout fitness profiles across hundreds of CRISPR screens, illuminating the modular organization of the cell.
Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin associationThis study suggests a novel role of the telomere-associated human CST complex in suppressing origin licensing, through interactions with MCM, while promoting the recruitment of AND-1 and DNA polymerase alpha for replisome formation.
An extracellular matrix protein promotes anillin-dependent processes in the Caenorhabditis elegans germlineThe extracellular matrix protein Hemicentin (HIM-4) is an extracellular factor that regulates anillin (ANI-1) for germ cell membrane stabilization and contractile ring formation in C. elegans germline cells.
Competition in the chaperone-client network subordinates cell-cycle entry to growth and stressGrowth and cell-cycle entry compete for multifunctional chaperones subjugating the critical size and proliferation to the growth potential of the cell.
Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunctionAberrant mitochondrial dynamics contribute to disease conditions. Genetic and pharmacological inhibition of USP8 ameliorates mitochondrial phenotypes deriving from loss of function of Drosophila PINK1 and Parkin.
The impact of poly-A microsatellite heterologies in meiotic recombinationMeiosis strongly influences the transmission and evolution of heterozygous poly-A repeats as measured experimentally in a large collection of single recombination products in a human hotspot.
Resources
Gene editing enables T-cell engineering to redirect antigen specificity for potent tumor rejectionTargeted integration of a tumor-reactive T-cell receptor into the TRAC locus using CRISPR-Cas9 and AAV6 redirects primary human T cells against tumor cells in vitro and in vivo.
Sequence and expression levels of circular RNAs in progenitor cell types during mouse corticogenesisThis study identifies circular RNAs (circRNAs) in specific cell types of the developing mammalian cortex. This resource addresses the complexity and potential significance of this elusive class of transcripts.
