Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination

Yoon, Je‐Hyun; Abdelmohsen, Kotb; Kim, Jiyoung; Yang, Xiaoling; Martindale, Jennifer L.; Tominaga-Yamanaka, Kumiko; White, Edward L.; Orjalo, Arturo V.; Rinn, John L.; Kreft, Stefan G.; Wilson, Gerald M.; Gorospe, Myriam

doi:10.1038/ncomms3939

Cited by 400 publications

(369 citation statements)

References 38 publications

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“…It has recently been reported that the lncRNA HOX transcript antisense RNA (HOTAIR) functions as a scaffold that enhances E3-mediated ubiquitination and degradation of substrate proteins (38). It has also been shown that lincRNA-p21, originally identified as a p53-inducible lncRNA that mediates p53-induced apoptosis in mouse cells (39), is a hypoxia-responsive lncRNA that plays a critical role in the regulation of hypoxia-enhanced glycolysis by inhibiting von Hippel-Lindau (VHL)-mediated hypoxia inducible factor 1 alpha (HIF1α) ubiquitination (40).…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Taniue

Kurimoto

Sugimasa

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

127

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Many long noncoding RNAs (lncRNAs) are reported to be dysregulated in human cancers and play critical roles in tumor development and progression. Furthermore, it has been reported that many lncRNAs regulate gene expression by recruiting chromatin remodeling complexes to specific genomic loci or by controlling transcriptional or posttranscriptional processes. Here we show that an lncRNA termed UPAT [ubiquitin-like plant homeodomain (PHD) and really interesting new gene (RING) finger domaincontaining protein 1 (UHRF1) Protein Associated Transcript] is required for the survival and tumorigenicity of colorectal cancer cells. UPAT interacts with and stabilizes the epigenetic factor UHRF1 by interfering with its β-transducin repeat-containing protein (TrCP)-mediated ubiquitination. Furthermore, we demonstrate that UHRF1 up-regulates Stearoyl-CoA desaturase 1 and Sprouty 4, which are required for the survival of colon tumor cells. Our study provides evidence for an lncRNA that regulates protein ubiquitination and degradation and thereby plays a critical role in the survival and tumorigenicity of tumor cells. Our results suggest that UPAT and UHRF1 may be promising molecular targets for the therapy of colon cancer.A mong the RNA products transcribed from the mammalian genome are numerous long noncoding RNAs (lncRNAs)-that is, RNAs longer than 200 nucleotides with little or no protein-coding potential (1, 2). Many lncRNAs are expressed in a developmentally regulated and cell type-dependent manner (3, 4). Increasing evidence suggests that lncRNAs play critical roles in a diverse set of biological processes, including proliferation, differentiation, embryogenesis, neurogenesis, and stem cell pluripotency (5, 6).It has been reported that many lncRNAs regulate gene expression by recruiting chromatin remodeling complexes to specific genomic regions (2). It has also been shown that many lncRNAs regulate transcription by modulating the activity of transcriptional regulators (1, 6-8). lncRNAs also regulate various posttranscriptional processes, including splicing, transport, translation, and degradation of mRNA. Furthermore, recent studies have shown that a number of lncRNAs play critical roles in tumor development and progression.UHRF1 [ubiquitin-like plant homeodomain (PHD) and really interesting new gene (RING) finger domain-containing protein 1] is an epigenetic factor that consists of multiple domains (9). UHRF1 regulates transcription by regulating DNA methylation and histone modification. UHRF1 also possesses E3 ubiquitin ligase activity and ubiquitinates histones and DNA methyltransferase 1 (DNMT1), thereby regulating the chromatin structure and stability of DNMT1 (10, 11). UHRF1 plays key roles in multiple biological processes, including proliferation and development. Furthermore, UHRF1 is overexpressed in various tumors, including colon, breast, bladder, prostate, and lung cancers, and plays a critical role in the proliferation and survival of tumor cells (9).In the present study, we attempted to identify lncRNAs criti...

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Taniue

Kurimoto

Sugimasa

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

127

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“…Some lncRNPs can affect gene expression at the transcriptional level; for example, lncRNA ANRIL represses p16INK4 transcription by interacting with the PRC2 complex at the INK4 locus, 24 and lncRNA GAS5 binds glucocorticoid receptors (GCRs) and thus acts as a decoy to prevent the transcriptional activity of GCRs. 25 Other lncRNPs can affect gene expression post-transcriptionally, 26 including the DNA damage-inducible lncRNA gadd7, which associates with the RBP TDP-43 and interferes with the ability of TDP-43 to stabilize CDK6 mRNA, 27 and LincRNA-RoR, which interacts with the RBP HNRNPI, an enhancer of TP53 production, and thus represses TP53 translation. 28 Similar to these examples, HuR-circRNA complexes (HuR circRNPs) may also influence the function of HuR by altering its ability to bind other target RNAs.…”

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confidence: 99%

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

et al. 2017

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HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding and noncoding linear RNAs. However, whether HuR binds to circular RNAs (circRNAs) and impacts on their function is unknown. Here, we have identified en masse circRNAs binding HuR in human cervical carcinoma HeLa cells. One of the most prominent HuR target circRNAs was hsa_circ_0031288, renamed CircPABPN1 as it arises from the PABPN1 pre-mRNA. Further analysis revealed that HuR did not influence CircPABPN1 abundance; interestingly, however, high levels of CircPABPN1 suppressed HuR binding to PABPN1 mRNA. Evaluation of PABPN1 mRNA polysomes indicated that PABPN1 translation was modulated positively by HuR and hence negatively by CircPABPN1. We propose that the extensive binding of CircPABPN1 to HuR prevents HuR binding to PABPN1 mRNA and lowers PABPN1 translation, providing the first example of competition between a circRNA and its cognate mRNA for an RBP that affects translation.

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“…This shows that the idea that Trim25 is using the RNA as a scaffold to get close to and modify RNP complexes might not limited to Trim proteins. This was also demonstrated by the E3 ligases Dzip3 and Mex3b which bind the long non-coding RNA HOTAIR, which acts as an RNA scaffold bringing them closer to their respective substrates, Ataxin-1 and Snurportin-1, leading to their ubiquitination [50].…”

Section: Trim25 Is An Rna-binding Proteinmentioning

confidence: 99%

The role of Trim25 in development, disease and RNA metabolism

Heikel

Choudhury

Michlewski

2016

Biochemical Society Transactions

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TUT -Terminal Uridylyltransferase AbstractTrim25 is a member of the tripartite motif family of E3 ubiquitin ligases. It plays major roles in innate immunity and defence against viral infection, control of cell proliferation and migration of cancer cells. Recent work identified Trim25 as being able to bind to RNA and to regulate Lin28a-mediated uridylation of pre-let-7. Here we review the current knowledge of the role of Trim25 in development, disease and RNA metabolism.

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Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination

Cited by 400 publications

References 38 publications

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

The role of Trim25 in development, disease and RNA metabolism

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