An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

Lin, Nianwei; Chang, Kung-Yen; Li, Zhonghan; Gates, Keith W.; Rana, Zacharia A.; Dang, Jason; Han, Tianxu; Yang, Chuan; Cunningham, Thomas J.; Head, Steven R.; Duester, Gregg; Dong, Peng; Rana, Tariq M.

doi:10.1016/j.molcel.2014.03.013

Cited by 55 publications

(74 citation statements)

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“…However, only 2 lincRNAs have been reported to promote reprogramming efficiency, lincRNA-RoR and TUNA [15,17], whilst lincRNAs that act as a barrier to reprogramming have not yet been identified. Understanding the repertoire of lincRNAs that regulate reprogramming and their roles is relevant because it could help to improve the reprogramming and also shed light on the role of the same lincRNAs in unrelated contexts, particularly in development.…”

Section: Discussionmentioning

confidence: 99%

“…LincRNA-RoR was the first lncRNA implicated in reprogramming [15] and partly functions as a 'sponge' that titrates down miRNAs targeting pluripotency regulators (e.g., miR-145) [16]. Conversely, lincRNA TUNA forms a complex with several RNA-binding proteins at the promoters of Nanog, Sox2 and Fgf4, where it facilitates the deposition of the active histone mark H3K4me3 [17].…”

Section: Introductionmentioning

confidence: 99%

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The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

et al. 2014

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Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

et al. 2014

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“…Most microarray-based transcriptome analyses will for example miss a large proportion of long noncoding RNAs (lncRNAs), which are involved in almost all known cellular processes (10)(11)(12)(13)(14), and are important in cancer biology, as shown by the number of functional characterized lncRNAs involved in carcinogenesis (15). In EAC, only two lncRNAs have been reported (16,17), and no systematic approach identifying lncRNAs dysregulation at different stages of Barrett's disease and EAC development has been published so far.…”

Section: Introductionmentioning

confidence: 99%

Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing

Mååg

Fisher

Levert-Mignon³

et al. 2017

Molecular Cancer Research

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Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is the main risk factor for EAC; however, the mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better understand this disease. Machine-learning and network analysis methods were applied to discover novel driver genes for EAC development. Identified gene expression signatures for the distinction of EAC from BE were validated in separate datasets. An extensive analysis of the noncoding RNA (ncRNA) landscape was performed to determine the involvement of novel transcriptomic elements in Barrett's disease and EAC. Finally, transcriptomic mutational investigation of genes that are recurrently mutated in EAC was performed. Through these approaches, novel driver genes were discovered for EAC, which involved key cell cycle and DNA repair genes, such as BRCA1 and PRKDC. A novel 4-gene signature (CTSL, COL17A1, KLF4, and E2F3) was identified, externally validated, and shown to provide excellent distinction of EAC from BE. Furthermore, expression changes were observed in 685 long noncoding RNAs (lncRNA) and a systematic dysregulation of repeat elements across different stages of Barrett's disease, with wide-ranging downregulation of Alu elements in EAC. Mutational investigation revealed distinct pathways activated between EAC tissues with or without TP53 mutations compared with Barrett's disease. In summary, transcriptome sequencing revealed altered expression of numerous novel elements, processes, and networks in EAC and premalignant BE.Implications: This study identified opportunities to improve early detection and treatment of patients with BE and esophageal adenocarcinoma. Mol Cancer Res; 15(11); 1558-69. Ó2017 AACR.

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“…Furthermore, a growing number of individual lncRNA candidates have been shown to be required for cellular differentiation and tissue development (Ulitsky et al 2011;Grote et al 2013;Kretz et al 2013;Ng et al 2013;Lin et al 2014;Zhao et al 2014). Conversely, several lncRNAs have been implicated in maintaining the pluripotent state of embryonic stem cells (ESCs) (Sheik Mohamed et al 2010;Guttman et al 2011;Lin et al 2014).…”

mentioning

confidence: 99%

Regulation of the ESC transcriptome by nuclear long noncoding RNAs

Bergmann

Eckersley-Maslin

et al. 2015

Genome Res.

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Long noncoding (lnc)RNAs have recently emerged as key regulators of gene expression. Here, we performed high-depth poly(A)+ RNA sequencing across multiple clonal populations of mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs) to comprehensively identify differentially regulated lncRNAs. We establish a biologically robust profile of lncRNA expression in these two cell types and further confirm that the majority of these lncRNAs are enriched in the nucleus. Applying weighted gene coexpression network analysis, we define a group of lncRNAs that are tightly associated with the pluripotent state of ESCs. Among these, we show that acute depletion of Platr14 using antisense oligonucleotides impacts the differentiation- and development-associated gene expression program of ESCs. Furthermore, we demonstrate that Firre, a lncRNA highly enriched in the nucleoplasm and previously reported to mediate chromosomal contacts in ESCs, controls a network of genes related to RNA processing. Together, we provide a comprehensive, up-to-date, and high resolution compilation of lncRNA expression in ESCs and NPCs and show that nuclear lncRNAs are tightly integrated into the regulation of ESC gene expression.

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An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

Cited by 55 publications

References 0 publications

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing

Regulation of the ESC transcriptome by nuclear long noncoding RNAs

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