Eukaryotic cell size regulation and its implications for cellular function and dysfunction

Physiological Reviews, Год журнала: 2024, Номер 104(4), С. 1679 - 1717

Опубликована: Июнь 20, 2024

Depending on cell type, environmental inputs, and disease, the cells in human body can have widely different sizes. In recent years, it has become clear that size is a major regulator of function. However, we are only beginning to understand how optimization function determines given cell’s optimal size. Here, review currently known control strategies eukaryotic intricate link intracellular biomolecular scaling, organelle homeostasis, cycle progression. We detail size-dependent regulation early development impact differentiation. Given importance for normal cellular physiology, must account changing conditions. describe sense stimuli, such as nutrient availability, accordingly adapt their by regulating growth Moreover, discuss correlation pathological states with misregulation long time this was considered downstream consequence dysfunction. newer studies reveal reversed causality, misregulated leading pathophysiological phenotypes senescence aging. summary, highlight important roles dysfunction, which could implications both diagnostics treatment clinic.

Язык: Английский

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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of the Drosophila wing disc

PLoS Genetics, Год журнала: 2024, Номер 20(9), С. e1011387 - e1011387

Опубликована: Сен. 3, 2024

A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D . melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Язык: Английский

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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of theDrosophilawing disc

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 14, 2024

Summary A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D. melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Язык: Английский

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Productive mRNA Chromatin Escape is Promoted by PRMT5 Methylation of SNRPB

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 10, 2024

Abstract Protein Arginine Methyltransferase 5 (PRMT5) regulates RNA splicing and transcription by symmetric dimethylation of arginine residues (Rme2s/SDMA) in many binding proteins. However, the mechanism which PRMT5 couples to transcriptional output is unknown. Here, we demonstrate that a major function activity promote chromatin escape novel, large class mRNAs term Genomically Retained Incompletely Processed Polyadenylated Transcripts (GRIPPs). Using nascent total transcriptomics, spike-in controlled fractionated cell proteomics, show inhibition knockdown SNRP (Sm protein) adapter protein pICln (CLNS1A) —but not type I PRMT inhibition—leads gross detention mRNA, SNRPB, SNRPD3 proteins on chromatin. Compared most transcripts, these chromatin-trapped polyadenylated transcripts have more introns, are spliced slower, enriched detained introns. combination inducible isogenic wildtype arginine-mutant methylation snRNPs critical for mediating their homeostatic interactions. Overall, conclude role controlling transcript processing completion subsequent nuclear export.

Язык: Английский

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mTOR potentiates senescent phenotypes and primary cilia formation after cisplatin-induced G2 arrest in retinal pigment epithelial cells

Cellular Signalling, Год журнала: 2024, Номер 124, С. 111402 - 111402

Опубликована: Сен. 7, 2024

Язык: Английский

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