Evidence for widespread cytoplasmic structuring into mesoscale condensates

Nature Cell Biology, Год журнала: 2024, Номер 26(3), С. 346 - 352

Опубликована: Фев. 29, 2024

Язык: Английский

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The Nuclear-to-Cytoplasmic Ratio: Coupling DNA Content to Cell Size, Cell Cycle, and Biosynthetic Capacity

Annual Review of Genetics, Год журнала: 2022, Номер 56(1), С. 165 - 185

Опубликована: Авг. 17, 2022

Though cell size varies between different cells and across species, the nuclear-to-cytoplasmic (N/C) ratio is largely maintained species within types. A maintains a relatively constant N/C by coupling DNA content, nuclear size, size. We explore how couple division growth to content. In some cases, use as molecular yardstick control availability of cycle regulators. other sets limit for biosynthetic capacity. Developmentally programmed variations in given type suggest that specific required respond physiological demands. Recent observations connecting decreased ratios with cellular senescence indicate maintaining proper essential functioning. Together, these findings causative, not simply correlative, role regulating progression.

Язык: Английский

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The integration of omics: A promising approach to personalized tuberculosis treatment

Medicine in Omics, Год журнала: 2024, Номер 12, С. 100033 - 100033

Опубликована: Янв. 13, 2024

Tuberculosis (TB) continues to be a global health problem due its high morbidity and death rates. Standardized regimens have been used in traditional TB treatment methods, frequently leading less-than-ideal results the establishment of drug-resistant strains. The development personalized medicine provides potentially effective remedy individual patients' by adjusting therapeutic approaches particular genotypic phenotypic traits. Detecting strains, drug resistance indicators, host genetic variants that affect is made possible genomic molecular diagnostic approaches. These developments offer helpful information for predicting therapy outcomes choosing best plan each individual. Integrating data, such as clinical characteristics, immunological state, comorbidities, improves decision-making accuracy. use targeted therapies, innovative anti-TB medicines repurposed medications, which potential overcome boost effectiveness, can guided therapy. Personalized interventions based on factors improve patient identifying those at risk failure or disease progression. This article discusses importance patients. It specifically highlights benefits using "omics" data enhance decrease resistance.

Язык: Английский

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Global control of RNA polymerase II

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Год журнала: 2024, Номер 1867(2), С. 195024 - 195024

Опубликована: Март 27, 2024

RNA polymerase II (Pol II) is the multi-protein complex responsible for transcribing all protein-coding messenger (mRNA). Most research on gene regulation focused mechanisms controlling which genes are transcribed when, or mechanics of transcription. How global Pol activity determined receives comparatively less attention. Here, we follow life a molecule from 'assembly complex' to nuclear import, enzymatic activity, and degradation. We focus how spends its time in nucleus, two-way relationship between abundance context homeostasis transcriptional changes.

Язык: Английский

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Changes in importin levels promote nuclear proteasomal degradation of cell cycle‐related proteins during THP‐1 monocyte‐to‐macrophage differentiation

FEBS Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Importin family nucleocytoplasmic transport receptors share thousands of cargo proteins. To elucidate cell regulatory mechanisms via regulation, we analyzed the levels by western blotting and quantified total cellular nuclear proteins during monocyte-to-macrophage differentiation THP-1 cells using mass spectrometry. Importin-α1 decreased importin-α5 increased differentiation. Cell cycle-related in both whole nuclei, proteasome-related nuclei but not cells. During with importin-α1 overexpression, some division-related recovered, knockdown, proteasome assembly factors nuclei. In this differentiation, reduce unnecessary abating import promoting proteasomal degradation. This study demonstrates importance global control regulation.

Язык: Английский

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Super-Resolution Mass Spectrometry Enables Rapid, Accurate, and Highly Multiplexed Proteomics at the MS2 Level

Analytical Chemistry, Год журнала: 2023, Номер 95(7), С. 3712 - 3719

Опубликована: Фев. 7, 2023

In tandem mass spectrometry (MS2)-based multiplexed quantitative proteomics, the complement reporter ion approaches (TMTc and TMTproC) were developed to eliminate ratio-compression problem of conventional MS2-level approaches. Resolving all high

Язык: Английский

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Single-cell proteomics: quantifying post-transcriptional regulation during development with mass-spectrometry

Development, Год журнала: 2023, Номер 150(13)

Опубликована: Июнь 30, 2023

ABSTRACT Many developmental processes are regulated post-transcriptionally. Such post-transcriptional regulatory mechanisms can now be analyzed by robust single-cell mass spectrometry methods that allow accurate quantification of proteins and their modification in single cells. These enable quantitative exploration protein synthesis degradation contribute to cell fate specification. Furthermore, they may support functional analysis conformations activities cells, thus link functions processes. This Spotlight provides an accessible introduction suggests initial biological questions ripe for investigation.

Язык: Английский

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Mitotic chromosomes scale to nuclear-cytoplasmic ratio and cell size in Xenopus

eLife, Год журнала: 2023, Номер 12

Опубликована: Апрель 25, 2023

During the rapid and reductive cleavage divisions of early embryogenesis, subcellular structures such as nucleus mitotic spindle scale to decreasing cell size. Mitotic chromosomes also decrease in size during development, presumably coordinately with spindles, but underlying mechanisms are unclear. Here we combine vivo vitro approaches using eggs embryos from frog Xenopus laevis show that chromosome scaling is mechanistically distinct other forms scaling. We found continuously cell, spindle, nuclear vivo. However, unlike for spindles nuclei, cannot be reset by cytoplasmic factors earlier developmental stages. In vitro, increasing nuclear-cytoplasmic (N/C) ratio sufficient recapitulate scaling, not or through differential loading maternal interphase. An additional pathway involving importin α scales surface area/volume (SA/V) metaphase. Finally, single-chromosome immunofluorescence Hi-C data suggest shrink embryogenesis decreased recruitment condensin I, resulting major rearrangements DNA loop architecture accommodate same amount on a shorter axis. Together, our findings demonstrate how set spatially temporally cues embryo.

Язык: Английский

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Principles of genome activation in the early embryo

Current Opinion in Genetics & Development, Год журнала: 2023, Номер 81, С. 102062 - 102062

Опубликована: Июнь 18, 2023

A major hurdle in an embryo's life is the initiation of its own transcriptional program, a process termed Zygotic Genome Activation (ZGA). In many species, ZGA intricately timed, with bulk transcription initiating at end series reductive cell divisions when cycle duration increases. At same time, changes genome architecture give rise to chromatin states that are permissive RNA polymerase II activity. Yet, we still do not understand events trigger gene expression right time and correct sequence. Here discuss new discoveries deepen our understanding how zygotic genes primed for transcription, these regulated by nuclear import. Finally, speculate on evolutionary basis timing as exciting future direction field.

Язык: Английский

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Karyopherin α2 is a maternal effect gene required for early embryonic development and female fertility in mice

The FASEB Journal, Год журнала: 2024, Номер 38(8)

Опубликована: Апрель 24, 2024

The nuclear transport of proteins plays an important role in mediating the transition from egg to embryo and distinct karyopherins have been implicated this process. Here, we studied impact KPNA2 deficiency on preimplantation development mice. Loss results complete arrest at 2cell stage embryos exhibit inability activate their embryonic genome as well a severely disturbed translocation Nucleoplasmin 2. Our findings define new maternal effect gene.

Язык: Английский

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