Plant Physiology and Biochemistry, Год журнала: 2025, Номер 221, С. 109618 - 109618
Опубликована: Фев. 11, 2025
Язык: Английский
Nature, Год журнала: 2024, Номер 630(8017), С. 720 - 727
Опубликована: Июнь 5, 2024
Abstract Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs) 1 , which influences offspring development adult phenotypes 1–7 . Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood 8 Here we used two distinct paradigms preconception acute high-fat diet dissect epididymal versus testicular contributions sperm sncRNA health. We show that spermatozoa, but developing germ cells, sensitive environment identify mitochondrial tRNAs (mt-tRNAs) their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs correlate with body mass index, paternal overweight at conception doubles obesity risk compromises metabolic Sperm sequencing mice mutant for genes involved function, phenotyping wild-type offspring, suggest upregulation downstream dysfunction. Single-embryo transcriptomics genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer mt-tRNAs fertilization suggested involvement control early-embryo transcription. Our study supports importance health metabolism, shows diet-induced demonstrates, physiological setting, father-to-offspring fertilization.
Язык: Английский
Процитировано
55
Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(15)
Опубликована: Апрель 1, 2024
Genomes are typically mosaics of regions with different evolutionary histories. When speciation events closely spaced in time, recombination makes the sharing same history small, and changes rapidly as we move along genome. examining rapid radiations such early diversification Neoaves 66 Mya, no consistent is observed across segments exceeding kilobases Here, report an exception. We found that a 21-Mb region avian genomes, mapped to chicken chromosome 4, shows extremely strong discordance-free signal for from inferred species tree. Such signal, indicative suppressed many millions base pairs, not elsewhere genome any deep relationships. Although long have been documented recently diverged species, our results pertain relationships dating circa 65 Mya. provide evidence this may be due ancient rearrangement blocked remained polymorphic several million years prior fixation. show presence has misled previous phylogenomic efforts lower taxon sampling, showing interplay between locus sampling. predict similar rearrangements confound phylogenetic analyses other clades, pointing need new analytical models incorporate possibility events.
Язык: Английский
Процитировано
17
Cell Reports, Год журнала: 2024, Номер 43(4), С. 114114 - 114114
Опубликована: Апрель 1, 2024
Patients afflicted with Stimulator of interferon gene (STING) gain-of-function mutations frequently present debilitating interstitial lung disease (ILD) that is recapitulated in mice expressing the STING
Язык: Английский
Процитировано
15
Nature Human Behaviour, Год журнала: 2025, Номер unknown
Опубликована: Янв. 3, 2025
Язык: Английский
Процитировано
2
Biology, Год журнала: 2025, Номер 14(1), С. 43 - 43
Опубликована: Янв. 8, 2025
It is becoming increasingly clear that microRNAs are key players in gene regulatory networks, modulating expression at post-transcriptional level. Their involvement almost all cellular processes predicts their role diseases, and several microRNA-based therapeutics currently undergoing clinical testing. Despite undeniable relevance the substantial body of literature demonstrating cancer other pathologies, identification functional interactions still challenging. To address this issue, resources have been developed to collect information from literature, according different criteria reliability scores. In present study, we constructed a network verified microRNA-mRNA by integrating strong-evidence couples resources. Our analysis resulting reveals only one-fifth human genes exhibits experimental validated regulation microRNAs. A very small subset them controlled more than 20 microRNAs, these hubs highly enriched pivotal transcription factors proteins, strongly suggesting complex interplay combinatorial effect between transcriptional control. Data also control multiple targets involved same pathway or biological process, likely contributing coordinated protein levels.
Язык: Английский
Процитировано
2
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 8, 2025
Abstract Post-translational modifications (PTMs) play pivotal roles in regulating cellular signaling, fine-tuning protein function, and orchestrating complex biological processes. Despite their importance, the lack of comprehensive tools for studying PTMs from a pathway-centric perspective has limited our ability to understand how modulate pathways on molecular level. Here, we present PTMNavigator, tool integrated into ProteomicsDB platform that offers an interactive interface researchers overlay experimental PTM data with pathway diagrams. PTMNavigator provides ~3000 canonical manually curated databases, enabling users modify create custom diagrams tailored data. Additionally, automatically runs kinase enrichment algorithms whose results are directly visualization. This view intricate relationship between signaling pathways. We demonstrate utility by applying it two phosphoproteomics datasets, showing can enhance analysis, visualize drug treatments result discernable flow PTM-driven aid proposing extensions existing By enhancing understanding dynamics facilitating discovery PTM-pathway interactions, advances knowledge biology its implications health disease.
Язык: Английский
Процитировано
2
Science Advances, Год журнала: 2025, Номер 11(2)
Опубликована: Янв. 8, 2025
Aerobic glycolysis is a hallmark of many viral infections, leading to substantial accumulation lactate. However, the regulatory roles lactate during infections remain poorly understood. Here, we report that human cytomegalovirus (HCMV) infection leverages induce widespread protein lactylation and promote spread. We establish lactyllysine enriched in intrinsically disordered regions, regulating condensates immune signaling transduction. Dynamic factors suppresses immunity, feature show be shared for HCMV herpes simplex virus 1 through regulation RNA binding 14 interferon-γ–inducible 16 (IFI16). K90 DNA sensor IFI16 inhibits recruitment damage response kinase DNA-PK, preventing IFI16-driven gene repression cytokine induction. Together, characterize global dynamics infection, finding virus-induced contributes its evasion direct inhibition pathways.
Язык: Английский
Процитировано
2
Nature Genetics, Год журнала: 2025, Номер unknown
Опубликована: Янв. 8, 2025
Abstract Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 genome assemblies (from 85 samples representing 38 Africans 47 non-Africans) in which majority autosomal are fully resolved using long-read assembly. Excluding acrocentric short arms sex chromosomes, we identify 173.2 Mb duplicated (47.4 not telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. find that intrachromosomal among most variable, with rare events mapping near their progenitor sequences. African genomes harbor more likely recently gene families higher copy numbers than non-African samples. Comparison resource 563 million full-length isoform sequencing reads identifies 201 novel, potentially protein-coding genes corresponding these number SDs.
Язык: Английский
Процитировано
2
Journal of Biological Chemistry, Год журнала: 2024, Номер 300(4), С. 107169 - 107169
Опубликована: Март 15, 2024
The unfolded protein response is a mechanism aiming at restoring endoplasmic reticulum (ER) homeostasis and likely involved in other adaptive pathways. transduced by three proteins acting as sensors triggering downstream signaling Among them, inositol-requiring enzyme 1 alpha (IRE1α) (referred to IRE1 hereafter), an reticulum-resident type I transmembrane protein, exerts its function through both kinase endoribonuclease activities, resulting X-box binding mRNA splicing RNA degradation (regulated ire1 dependent decay). An increasing number of studies have reported protein-protein interactions regulators these mechanisms, additionally, driving noncanonical functions. In this review, we deliver evolutive structural insights on further describe how interaction network (interactome) regulates abilities or mediates cellular processes catalytic-independent mechanisms. Moreover, focus newly discovered targets activity discuss potentially novel functions based the nature interactome, thereby identifying new fields explore regarding protein's biological roles.
Язык: Английский
Процитировано
12
Molecular Cell, Год журнала: 2024, Номер 84(15), С. 2870 - 2881.e5
Опубликована: Июль 15, 2024
The human silencing hub (HUSH) preserves genome integrity through the epigenetic repression of invasive genetic elements. However, despite our understanding HUSH as an obligate complex three subunits, only loss MPP8 or Periphilin, but not TASOR, triggers interferon signaling following derepression endogenous retroelements. Here, we resolve this paradox by characterizing a second that shares and Periphilin assembles around TASOR2, uncharacterized paralog TASOR. Whereas represses LINE-1 retroelements marked repressive histone modification H3K9me3, HUSH2 is recruited transcription factor IRF2 to repress interferon-stimulated genes. Mechanistically, HUSH-mediated retroelement sequesters limited pool shared subunits preventing TASOR2 from forming complexes hence relieving HUSH2-mediated Thus, competition between two intertwines with induction immune response, coupling aspects defense.
Язык: Английский
Процитировано
11