Cytoplasmic translocation of tumor suppressor HINT1 and its impact on cell shape during density transition
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1129113 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cells at low density exhibit spreading and migration behaviors with more spread-out morphologies, while high-density cultures show confined, rounded morphologies. During this transition, the actin cytoskeleton rearranges from oriented stress fibers to a cortical actin shell, supporting cell movement and shape maintenance. This transition also halts cell proliferation to prevent uncontrolled growth, as seen in tumors. However, the molecular mechanism behind actin cytoskeleton remodeling by cell density is not well understood. Using proteomics of purified open chromatin, we identified the tumor suppressor HINT1 as a key molecule whose nucleocytoplasmic shuttling depends on cell density. RNA-seq analysis of wild-type (WT) and knock-out (KO) HEK293A cells revealed that HINT1 is involved in morphogensis and development.
2025-07-14 | GSE270956 | GEO
Project description:Developmental Cytoplasmic-to-Nuclear Translocation of RNA-Binding Protein HuR Is Required for Adult Neurogenesis
| PRJNA565168 | ENA
Project description:Although neurogenesis in the adult brain recapitulates processes that occur during embryonic development, adult neurogenesis exhibits distinct characteristics from its embryonic counterpart. However, the intrinsic mechanism underlying the differential regulation of neurogenesis between these two stages remains unclear. Herein, we show that the ablation of RNA-binding protein HuR in neural stem cells (NSCs) impairs adult, but not embryonic, neurogenesis. HuR is predominantly expressed in the cytoplasm of embryonic NSCs but translocates into the nucleus of adult NSCs. Transcriptomic analysis of HuR-deficient adult NSCs revealed that nuclear HuR primarily regulates alternative splicing of numerous premRNA transcripts, including focal adhesion kinase (FAK). HuR-deficient adult NSCs generate increased FAK mRNA isoforms with shorter 5’ UTRs, leading to enhanced FAK mRNA translation and hyperactivated FAK signaling, and inhibition of FAK ameliorates defective adult neurogenesis and impaired hippocampus-dependent learning in HuR-deficient mice. Taken together, these findings reveal novel mechanistic insights into the differential regulation of embryonic and adult neurogenesis through developmental cytoplasmic-to-nuclear translocation of HuR in NSCs.
2019-11-04 | GSE137323 | GEO
Project description:Long noncoding RNAs (lncRNAs) have potential as novel therapeutic targets in cardiac disease, but their function in heart failure (HF) is not yet fully understood. Using a gene trapping approach in mouse embryonic stem cells, we identified a novel cytoplasmic lncRNA, dubbed Caren (cardiomyocyte-enriched noncoding transcript), which was predominantly expressed in cardiomyocytes. Caren was markedly downregulated in the mouse failing heart that was subjected to transverse aortic constriction (TAC). The ablation of Caren in the mouse heart accelerated HF-related phenotypes by TAC, whereas mice overexpressing Caren (CAG-Caren Tg mice) resisted TAC-induced HF. Proteomic analysis identified histidine triad nucleotide-binding protein 1 (Hint1) as a Caren target protein, while bioinformatic analysis of proteome revealed that Caren regulates the proteins involved in mitochondrial energetics in the heart. Furthermore, we found that Caren suppressed Hint1 expression at the translational level and that Hint1 overexpression reduced mitochondrial respiration capacity. Similar to CAG-Caren Tg mice, the reduced Hint1 expression in mice exerted cardioprotective effects on TAC-induced HF, which was associated with the decreased level of ATM serine/threonine kinase phosphorylation, known to activate DNA damage responses. Overall, we identify a novel cytoplasmic lncRNA that protects against the development of HF through suppressing the Hint1-ATM signaling, which presumably maintains mitochondrial energetics and prevents the DNA damage under pathological stress.
2021-02-08 | PXD016186 | Pride
Project description:The goal of this study was to understand the underlying structure of nucleotides 403-780 of the lncRNA SLNCR1, in-cell and when extracted from nuclear and cytoplasmic fractions. SHAPE and DMS probing revealed that the region is largely unstructured inside and outside of the cell, and appears protein-bound in primary melanoma cells.
2019-11-07 | GSE140048 | GEO
Project description:ERCC6L2 suppresses chromosome translocation
| PRJNA1184159 | ENA
Project description:Binding of transcription factors to DNA is mediated by the recognition of the chemical signatures of the DNA bases and the three-dimensional shape of the DNA molecule. The direct contribution of DNA shape to DNA-binding specificity has been difficult to assess, as DNA shape is a consequence of its sequence. Here, we teased apart these two modes of recognition in the context of Hox-DNA binding. We made a series of mutations in Hox residues that, in a co-crystal structure, only recognize DNA shape, and tested the effect on DNA binding preferences using SELEX-seq. Analysis of shape features of selected sequences revealed that these residues are both necessary and sufficient for selection of sequences with distinct shape features. We used statistical machine learning to show that the accuracy of binding specificity predictions improves by adding shape features to a model that only depends on sequence. We conclude that shape readout is a direct and critical component of binding site selection by Hox proteins. Three rounds of SELEX were performed on a series of Hox mutants as described in Slattery et al, Cell, 2011 (PMID 22153072) and Riley et al, Methods in molecular Biology, 2014 (PMID 25151169). Briefly, His-tagged Scr and Antp mutant proteins were incubated with a randomized 16mer oligonucleotide library, and bound DNA was amplified and sequenced as described (PMID 22153072, PMID 25151169).
2015-01-21 | E-GEOD-65073 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE30202: DNA binding factors shape the mouse methylome at distal regulatory regions [BIS_seq] GSE30203: DNA binding factors shape the mouse methylome at distal regulatory regions [ChIP-seq] GSE30204: DNA binding factors shape the mouse methylome at distal regulatory regions [ChIP_chip] GSE30280: DNA binding factors shape the mouse methylome at distal regulatory regions [RNA_seq] Refer to individual Series
2011-12-09 | E-GEOD-30206 | biostudies-arrayexpress