Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Disruption of ZC3H15 Compromises Telomere Length Maintenance by Sequestering Telomerase within Cajal bodies

ABSTRACT: Telomere homeostasis, crucial for various biological processes, relies on telomerase activity. We identified ZC3H15 as a novel telomerase-interacting protein. Its deletion unexpectedly increased telomerase activity but led to shortened telomeres and cellular senescence. ZC3H15 interacts with telomerase and itself, regulating telomerase activity in an RNA-dependent manner. Proximity labeling showed ZC3H15's interaction with proteins involved in organelle assembly and RNA processes. Loss of ZC3H15 sequestered TERC in the Cajal body, reducing telomerase recruitment to telomeres during S phase. These findings unveil ZC3H15's role in telomere dynamics and cellular senescence, suggesting its potential as a target for cancer therapy or anti-aging interventions.

ORGANISM(S): Homo Sapiens

SUBMITTER: Yan Huang

PROVIDER: PXD052036 | iProX | Mon May 06 00:00:00 BST 2024

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

Disruption of ZC3H15 compromises telomere length maintenance by entrapping telomerase within cajal bodies.

Wang Chuanle C Chen Wei W Li Ruofei R Yang Yue Y Wu Jiali J Tian Yuyang Y He Zibin Z Lin Song S Wang Xining X Zhu Jianxi J Ma Wenbin W Songyang Zhou Z Huang Yan Y

Cell & bioscience 20250722 1

<h4>Background</h4>Telomere homeostasis is pivotal in various biological processes including ontogeny, reproduction, physiological aging, and the onset of numerous diseases such as tumors. In human stem cells and approximately 85% of tumor cells, telomerase formed by TERT and TERC RNA complex is responsible for elongating telomeres. However, the intricate and precise regulatory mechanisms governing telomerase remain largely elusive.<h4>Methods and results</h4>We developed a genome-wide trimolecu ...[more]

PMID: 40696438

Similar Datasets

IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis

Project description:Cytosolic dsDNA surveillance by cGAS-STING signaling triggers autophagy, biased mRNA translation, cellular senescence, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that IRF3, activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a well-known tumor suppressor and key cell cycle regulator. The IRF3-RB interaction attenuates CDK4/6-mediated hyperphosphorylation of RB that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in hepatic stellate cells (HSCs) within CCl4 or bile duct ligation (BDL)-induced murine models, pushing activated HSCs towards senescence. Accordingly, global IRF3 knockout or conditional deletion of IRF3 in HSCs aggravated liver fibrosis, a process mitigated by an FDA-approved CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis.

2024-12-31 | GSE252219 | GEO

Localization of HIRA in PML bodies is tightly linked SASP expression

Project description:Cellular senescence, a stable proliferation arrest caused by a range of cellular stresses, is a bona fide cause of cell and tissue aging. As well as proliferation arrest, cell senescence is associated with a potent pro-inflammatory phenotype, the senescence-associated secretory phenotype (SASP). Given that SASP is regulated at various levels, gaining a comprehensive understanding of its regulation is crucial. This understanding can pave the way for potential therapeutic approaches aimed at modulating SASP, which could promote healthy aging and alleviate the burden of senescence-associated diseases and degeneration. We show here that both the Promyelocytic Leukemia (PML) protein and HIRA histone chaperone are required for SASP expression in senescent cells. PML protein is the key organizer of PML nuclear bodies, nuclear features up to 1mM in diameter, containing many proteins and previously implicated in diverse cellular processes, including control of cell senescence and cellular intrinsic anti-viral immunity. HIRA is a histone chaperone best known for its ability to incorporate histone variant H3.3 into nuclear chromatin in a DNA replication-independent manner, including in non-proliferating senescent cells. HIRA localizes to PML nuclear bodies in senescent cells. We show that both HIRA and PML are required for activation of NF-kB and SASP. We found that HIRA regulates cytoplasmic NF-kB signaling in senescent cells through CCF-cGAS-STING-TBK1 pathway and interaction with autophagy cargo receptor Sequestosome-1 (p62/SQSTM1).

2024-08-13 | GSE233847 | GEO

Cellular senescence and its associated AKR1B1 promote cyst growth in ADPKD

Project description:Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited kidney diseases. Cellular senescence regulates not only physiological and homeostatic processes, particularly during embryonic development and wound healing, but also pathological processes that contribute to aging, cancer, and other diseases in response to endogenous and exogenous stresses. However, the role of cellular senescence in ADPKD remains elusive. To determine whether D-gal induces differential senescence response in Pkd1-null vs. wild-type cells, we performed RNA-sequencing (RNA-seq) analysis.

2025-03-29 | GSE292808 | GEO

Nuclear barrier induction as a new modality of cellular senescence

Project description:Blocking of nucleocytoplasmic trafficking is an essential feature of replicative senescence (RS). However, whether nuclear barrier per se causes cellular senescence still remains elusive. Here, we show that nuclear barrier induced by blocking nucleocytoplasmic trafficking, especially nuclear export, elicits RS-like changes in SA-β-gal activity, DNA damage, and expression of cell cycle regulators. Comparative transcriptome analysis revealed that nuclear barrier-induced senescence (NBIS) was most similar in gene expression changes to RS compared to senescence induced by stresses (oxidative stress, DNA damage and oncogene), implying that nuclear barrier induces RS-like physiological senescence-associated changes. Shared senescence-related processes between NBIS and RS included lysosomal degradation, nuclear transport, and translation, resulting in coordinated reduction in transmission of extrinsic signals to nucleus and intracellular protein supply from nucleus. Notably, these processes were conserved in yeast aging. Therefore, we propose NBIS as a novel modality of cellular senescence, representing the fundamental nature of physiological aging in eukaryotes.

2021-06-17 | GSE112530 | GEO

Distinct translational control in CD4+ T-cell subsets

Project description:Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression-studies have defined canonical signatures of T-cell subsets. Changes in steady-state mRNA levels do, however, often not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4+Foxp3+ regulatory T (TFoxp3+) and CD4+Foxp3- non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T-cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both TFoxp3- and TFoxp3+ cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4+ T-cell subset. CD4+/Foxp3+ and CD4+Foxp3- cells were studied ex vivo or activated in vitro for 36h. Both polysome-associated and cytoplasmic RNA was isolated to enables studies of translational control

2013-06-01 | E-GEOD-45401 | biostudies-arrayexpress

Gene expression profiling of Elastin (ELN) knock-down in human fibroblast MRC5

Project description:The ELN gene encodes tropoelastin which is used to generate elastic fibers that insure proper tissue elasticity. Decreased amounts of elastic fibers and/or accumulation of bioactive products of their cleavage, named elastokines, are thought to contribute to aging. Cellular senescence, characterized by a stable proliferation arrest and by the senescence-associated secretory phenotype (SASP), increases with aging. Here, we identified that decrease in ELN either by siRNA in normal human fibroblasts results in premature senescence. Surprisingly this effect is independent of elastic fiber degradation or elastokines production, but it relies on the rapid increase in HMOX1 after ELN downregulation. These results unveil a role for ELN in protecting cells from cellular senescence through a non-canonical mechanism.

2024-05-30 | GSE268042 | GEO

PRDM16 restricts cellular senescence by upregulating GSTM1

Project description:Cellular senescence is a hallmark of aging, and the accumulation of senescent cells (SnCs) accelerates the aging process and contributes to aging-related organ disorders. The PRDMs exhibit robust transcriptional regulatory activity and govern a wide range of biological processes. However, the role of PRDMs in cellular senescence and aging remain unclear. Here, we have demonstrated that PRDM16, among PRDMs, is decreased significantly in multiple organs of aged mice compared to young mice. Global Prdm16 deletion contributes to cellular senescence in various organs, including the kidney, heart, lung, brain hippocampus, stomach, and gut; subsequently leading to accelerated aging-related organ injury. Furthermore, tubular specific Prdm16 deletion aggravates irradiation induced kidney aging, and aging-related kidney disease subjected to ischemia reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuates cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improves glutathione metabolism and inhibits oxidative DNA damage, the driving force of senescence. Especially, PRDM16 increases glutathione-S-transferase activity by upregulating the transcription of GSTM1. Transfection of GSTM1 restored cellular senescence and kidney aging caused by PRDM16 deficiency. Taken together, we provide a potential target for investigating the anti-aging therapy.

2025-08-25 | GSE275768 | GEO

LARP7 ameliorates cellular senescence and aging-related atherosclerosis by allosterically enhancing SIRT1 deacetylase activity

Project description:Cell senescence is a cell state characterized with permanent cell cycle arrest and elevated proinflammatory secretome and associated with pleiotropic essential physiopathological processes. The persistent DNA damage response (DDR) is the major stress leading to senescence, however the molecular mechanism underling remains elusive. Here, we identified the La Ribonucleoprotein 7 (LARP7), a 7SK RNA binding protein, as a novel SIRT1 deacetylase activator. It directly interacted with SIRT1 allosteric regulatory domain and enhanced its deacetylase activity. DDR-mediated ATM activation trigged the extracellular shuttling and downregulation of LARP7 that dampened the SIRT1 deacetylase activity and enhanced p53 and NFB (p65) transcriptional activity by augmenting their acetylation. As a consequence, activated p53 and NFB arrested cell growth and promoted SASP genes expression, and thereby accelerated the cellular senescence. Inducible deletion of LARP7 in wildtype mouse led to senescent cell accumulation and premature ageing. Furthermore, we identified that ATM-LARP7-SIRT1-p53/NFB senescent axis was active in the aortic senescence and atherogenesis. Genetic depletion of LARP7 aggravated the atherogenesis but conversely, inhibited ATM activation or restoring LARP7 expression with genetic manipulation alleviated the vascular aging and atherogenesis. Together, this study identifies LARP7 as a novel SIRT1 cellular activator and it’s-mediated ATM-LARP7-SIRT1-p53/NFB axis is attributed to DDR-mediated cellular senescence and aging-related pathologies.

2021-10-30 | GSE160279 | GEO

GNPS Metabolomics Profiling of Single Enlarged Lysosomes Defines the Molecular Signature of Lysosomal Heterogeneity

Project description:Lysosomes are critical for cellular metabolism and heterogeneously involved in various cellular processes such as endocytosis, autophagy and senescence. The ability to measure lysosomal metabolic heterogeneity is essential for understanding its physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nanoESI/MS that enabled concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes.

2021-04-14 | MSV000087208 | GNPS

Single cell data from mechanically-loaded muscle

Project description:Skeletal muscle has abilities to regenerate after injuries and adapt to mechanical loadings. Compared with the regenerative processes, the cellular networks in the loaded muscles have not been well-explored. In this analyses, we did single-cell RNA sequencing to unveil the gene expression signature of individual cells and the cellular networks in surgically overloaded muscle.

2024-03-11 | GSE232257 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data