TINCR lncRNA encodes a ubiquitin-like protein that activates CDC42, promotes epithelial differentiation and suppresses tumor growth
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA732428 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14634139_1.fastq.gz | Fastqsanger.gz | |||
| SRR14634139_2.fastq.gz | Fastqsanger.gz | |||
| SRR14634140_1.fastq.gz | Fastqsanger.gz | |||
| SRR14634140_2.fastq.gz | Fastqsanger.gz | |||
| SRR14634141_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 116 |
Similar Datasets
Project description:The human transcriptome contains thousands of small open reading frames (sORFs) that have been largely overlooked because of their small size. Some of these sORFs code for bioactive small proteins although none have been associated to the regulation of cell identity. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein with a SUMO interacting motif (SIM) that is expressed in many epithelia. pTINCR binds to SUMO and modifies global cell SUMOylation patterns. One of its main targets is CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and for epidermal differentiation. pTINCR increases CDC42 SUMOylation and promotes its activation in a SIM-dependent manner. pTINCR is necessary and sufficient for epithelial cell differentiation in vitro, and promotes epidermal differentiation in vivo. Consistent with its pro-differentiation role, pTINCR expression is lost in human cutaneous squamous cell carcinomas (cSCC), and its overexpression reduces cSCC growth in vitro and in vivo. Moreover, pTINCR is a target of the tumor suppressor p53, and the expression of pTINCR in epithelial cancers correlates with better prognosis. Our results identify pTINCR as a novel regulator of epithelial differentiation with tumor suppressor activity. More generally, our findings suggest that the proteome encoded by previously assumed non-coding RNAs can indeed be a source of new regulators of cell identity relevant for cancer.
2022-09-28 | GSE175463 | GEO
Project description:The human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation and under cellular stress. By gain- and loss-of-function studies, we demonstrate that pTINCR is a key inducer of epithelial differentiation in vitro and in vivo. Interestingly, low expression of TINCR associates with worse prognosis in several epithelial cancers, and pTINCR overexpression reduces malignancy in patient-derived xenografts. At the molecular level, pTINCR binds to SUMO through its SUMO interacting motif (SIM) and to CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and epithelial differentiation. Moreover, pTINCR increases CDC42 SUMOylation and promotes its activation, triggering a pro-differentiation cascade. Our findings suggest that the microproteome is a source of new regulators of cell identity relevant for cancer.
2022-10-06 | PXD026181 | Pride
Project description:Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7kb lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high mRNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a suite of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25 nucleotide M-bM-^@M-^\TINCR boxM-bM-^@M-^] motif which is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyze TINCR binding capacity to ~9,400 human recombinant proteins revealed direct binding of TINCR RNA to the Staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay (SMD), however, lacked differentiation impacts. Instead, the TINCR/STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through inducible lncRNA binding to differentiation mRNAs to ensure their expression. Examination of TINCR-binding RNAs using two independent pools of TINCR-targeting oligos
2012-10-10 | E-GEOD-40121 | biostudies-arrayexpress
Project description:Purpose: Identify RNA interactome of lncRNA TINCR Methods: Primary melanoma cell lines WM902B and MMC70 lysates hybridized with TINCR antisense DNA oligos Results: we found that TINCR silencing induces activation of translation of ATF4 and other stress responsive RNAs.
2020-11-25 | GSE125833 | GEO
Project description:In order to study the mechanism of TINCR affecting development of HCC, TINCR in liver cancer stem cells was knocked down. RNA-seq was employed to explore the potential target genes and signaling pathways.
2022-10-21 | GSE215894 | GEO
Project description:Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7kb lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high mRNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a suite of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25 nucleotide “TINCR box” motif which is strongly enriched in interacting mRNAs \and required for TINCR binding. A high-throughput screen to analyze TINCR binding capacity to ~9,400 human recombinant proteins revealed direct binding of TINCR RNA to the Staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay (SMD), however, lacked differentiation impacts. Instead, the TINCR/STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through inducible lncRNA binding to differentiation mRNAs to ensure their expression. Gene expression analysis: To establish a gene expression signature for regenerated human epidermis depleted of TINCR, as well as STAU1, total RNA was isolated in biologic duplicate from organotypic cultures of cells with a non-targeting siRNA, or an siRNA to the gene of interest. This RNA was processed and then hybridized to Affymetrix HG-U133 2.0 Plus arrays.
2012-10-10 | E-GEOD-40122 | biostudies-arrayexpress
Project description:Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7kb lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high mRNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a suite of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25 nucleotide “TINCR box” motif which is strongly enriched in interacting mRNAs \and required for TINCR binding. A high-throughput screen to analyze TINCR binding capacity to ~9,400 human recombinant proteins revealed direct binding of TINCR RNA to the Staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay (SMD), however, lacked differentiation impacts. Instead, the TINCR/STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through inducible lncRNA binding to differentiation mRNAs to ensure their expression.
2012-10-10 | GSE40122 | GEO
Project description:Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7kb lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high mRNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a suite of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25 nucleotide “TINCR box” motif which is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyze TINCR binding capacity to ~9,400 human recombinant proteins revealed direct binding of TINCR RNA to the Staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay (SMD), however, lacked differentiation impacts. Instead, the TINCR/STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through inducible lncRNA binding to differentiation mRNAs to ensure their expression.
2012-10-10 | GSE40121 | GEO
Project description:Purpose: Study the changes in cell transcriptome upon overexpression of lncRNA TINCR Methods: Primary melanoma cell line WM902B was transduced with lientiviruses expressing Scrambled and TINCR directed shRNA hairpins Results: we found that TINCR overexpression induces partial reversion of invasive phenotype
2020-11-25 | GSE125834 | GEO
Project description:Purpose: Study the changes in mRNA translation upon silencing of lncRNA TINCR Methods: Primary melanoma cell line WM902B was transduced with lientiviruses expressing Scrambled and TINCR directed shRNA hairpins Results: we found that TINCR silencing induces activation of ATF4 translation
2020-11-25 | GSE125832 | GEO