The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

Abdalla, Mohamed; Yamamoto, Takaya; Maehara, Kazuhira; Nogami, Jumpei; Ohkawa, Yasuyuki; Miura, Hisashi; Poonperm, Rawin; Hiratani, Ichiro; Nakayama, Hideki; Nakao, Mitsuyoshi; Saitoh, Noriko

doi:10.1038/s41467-019-11378-4

Cited by 31 publications

(32 citation statements)

References 70 publications

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“…Suppression of Eleanor RNAs reduces the ESR1 transcription. Therefore, Eleanors may be a good therapeutic target for breast cancers 25,43,44 . However, the mechanism by which Eleanor RNAs stimulate the ESR1 transcription has remained enigmatic.…”

Section: Discussionmentioning

confidence: 99%

Nucleosome destabilization by nuclear non-coding RNAs

et al. 2020

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In the nucleus, genomic DNA is wrapped around histone octamers to form nucleosomes. In principle, nucleosomes are substantial barriers to transcriptional activities. Nuclear noncoding RNAs (ncRNAs) are proposed to function in chromatin conformation modulation and transcriptional regulation. However, it remains unclear how ncRNAs affect the nucleosome structure. Eleanors are clusters of ncRNAs that accumulate around the estrogen receptor-α (ESR1) gene locus in long-term estrogen deprivation (LTED) breast cancer cells, and markedly enhance the transcription of the ESR1 gene. Here we detected nucleosome depletion around the transcription site of Eleanor2, the most highly expressed Eleanor in the LTED cells. We found that the purified Eleanor2 RNA fragment drastically destabilized the nucleosome in vitro. This activity was also exerted by other ncRNAs, but not by poly(U) RNA or DNA. The RNA-mediated nucleosome destabilization may be a common feature among natural nuclear RNAs, and may function in transcription regulation in chromatin.

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Section: Discussionmentioning

confidence: 99%

Nucleosome destabilization by nuclear non-coding RNAs

et al. 2020

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“…ELEANORS also play a role in mediating long-range chromatin interactions and balancing between cell proliferation and apoptosis. 64…”

Section: Aberrant Nuclear Microenvironment Is Created Through Llps mentioning

confidence: 99%

Nuclear microenvironment in cancer: Control through liquid‐liquid phase separation

et al. 2020

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The eukaryotic nucleus is not a homogenous single‐spaced but a highly compartmentalized organelle, partitioned by various types of membraneless structures, including nucleoli, PML bodies, paraspeckles, DNA damage foci and RNA clouds. Over the past few decades, these nuclear structures have been implicated in biological reactions such as gene regulation and DNA damage response and repair, and are thought to provide “microenvironments,” facilitating these reactions in the nucleus. Notably, an altered morphology of these nuclear structures is found in many cancers, which may relate to so‐called “nuclear atypia” in histological examinations. While the diagnostic significance of nuclear atypia has been established, its nature has remained largely enigmatic and awaits characterization. Here, we review the emerging biophysical principles that govern biomolecular condensate assembly in the nucleus, namely, liquid‐liquid phase separation (LLPS), to investigate the nature of the nuclear microenvironment. In the nucleus, LLPS is typically driven by multivalent interactions between proteins with intrinsically disordered regions, and is also facilitated by protein interaction with nucleic acids, including nuclear non–coding RNAs. Importantly, an altered LLPS leads to dysregulation of nuclear events and epigenetics, and often to tumorigenesis and tumor progression. We further note the possibility that LLPS could represent a new therapeutic target for cancer intervention.

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“…Therefore, u-Eleanor may be used as a biomarker of breast cancer at early stages [116]. Furthermore, a recent study has revealed the function of another Eleanor called promoter-associated Eleanor (pa-Eleanor), which is transcribed from the region proximal to the transcriptional start site of ESR1 [120]. In the nucleus, chromosomes fold into domains called topologically associating domains (TADs), which exhibit intra-chromatin interactions [121].…”

Section: Lncrnas Belonging To Multiple Categoriesmentioning

confidence: 99%

Long Noncoding RNAs Involved in the Endocrine Therapy Resistance of Breast Cancer

Takeiwa

Ikeda

Mitobe

et al. 2020

Cancers

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Long noncoding RNAs (lncRNAs) are defined as RNAs longer than 200 nucleotides that do not encode proteins. Recent studies have demonstrated that numerous lncRNAs are expressed in humans and play key roles in the development of various types of cancers. Intriguingly, some lncRNAs have been demonstrated to be involved in endocrine therapy resistance for breast cancer through their own mechanisms, suggesting that lncRNAs could be promising new biomarkers and therapeutic targets of breast cancer. Here, we summarize the functions and mechanisms of lncRNAs related to the endocrine therapy resistance of breast cancer.

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The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

Cited by 31 publications

References 70 publications

Nucleosome destabilization by nuclear non-coding RNAs

Nucleosome destabilization by nuclear non-coding RNAs

Nuclear microenvironment in cancer: Control through liquid‐liquid phase separation

Long Noncoding RNAs Involved in the Endocrine Therapy Resistance of Breast Cancer

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