Advances in understanding chromosome silencing by the long non-coding RNA Xist

Sado, Takashi; Brockdorff, Neil

doi:10.1098/rstb.2011.0325

Cited by 55 publications

(47 citation statements)

References 88 publications

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“…XIST RNA is the paradigm for an RNA that binds and regulates chromatin (Figure 1A) [1–4] and is well reviewed elsewhere [5–7]. Here, we limit our discussion of XIST RNA and female X-inactivation to a few points related to the broader role of RNA in chromatin and the potential involvement of repeat-rich DNA and RNA.…”

Section: Insights From Xist Rna and A Paradox Of The Barr Bodymentioning

confidence: 99%

RNA as a fundamental component of interphase chromosomes: could repeats prove key?

Hall

Lawrence

2016

Current Opinion in Genetics & Development

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Beginning with the precedent of XIST RNA as a “chromosomal RNA” (cRNA), there is growing interest in the possibility that a diversity of non-coding RNAs may function in chromatin. We review findings which lead us to suggest that RNA is essentially a widespread component of interphase chromosomes. Further, RNA likely contributes to architecture and regulation, with repeat-rich “junk” RNA in euchromatin (ecRNA) promoting a more open chromatin state. Thousands of low-abundance nuclear RNAs have been reported, however it remains a challenge to determine which of these may function in chromatin. Recent findings indicate that repetitive sequences are enriched in chromosome-associated non-coding RNAs, and repeat-rich RNA shows unusual properties, including localization and stability, with similarities to XIST RNA. We suggest two frontiers in genome biology are emerging and may intersect: the broad contribution of RNA to interphase chromosomes and the distinctive properties of repeat-rich intronic or intergenic junk sequences that may play a role in chromosome structure and regulation.

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Section: Insights From Xist Rna and A Paradox Of The Barr Bodymentioning

confidence: 99%

RNA as a fundamental component of interphase chromosomes: could repeats prove key?

Hall

Lawrence

2016

Current Opinion in Genetics & Development

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“…4 While small ncRNA species like miRNA, siRNA, piRNA, were shown to predominantly inhibit target gene expression by complementary base pairing, 5 much less is known about the role of lncRNAs. Although the functions of some lncRNAs such as Xist 6,7 have been well characterized, research on the majority of lncRNAs remains scarce due to a lack of efficient genome editing tools for deletion of large genomic regions. Recently, successful deletion of malat1, a lncRNA in zebrafish, using the TALEN system 8 was reported, while the CRISPR/Cas9 system is seeing increasing use for gene editing.…”

Section: Introductionmentioning

confidence: 99%

Efficient in vivo deletion of a large imprinted lncRNA by CRISPR/Cas9

et al. 2014

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“…Many lncRNAs are expressed at specific times and in specific tissues during development, and exhibit a variety of slicing patterns. It has been proposed that lncRNAs are involved in the epigenetic regulation of coding genes, and thus exert a powerful effect on a number of physiological and pathological processes, including the pathogenesis of many human cancers [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells

Zhang

Han

et al. 2014

J Exp Clin Cancer Res

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Prostate cancer gene expression marker 1 (PCGEM1) is a long non-coding RNA (lncRNA) overexpressed in prostate cancer (PCa) cells that promotes PCa initiation and progression, and protects against chemotherapy-induced apoptosis. The microRNA miR-145 functions as a tumor suppressor in PCa. We speculate that reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells. To test this hypothesis, the interaction between PCGEM1 and miR-145 was examined using a luciferase reporter assay. Expression levels were selectively altered in LNCaP cells and noncancerous RWPE-1 prostate cells by transfection of miR-145 or small interfering RNA sequences against (siRNA) PCGEM1. Relative expression levels were detected by RT-PCR, tumor cell growth and early apoptosis by the MTT assay and flow cytometry, respectively, and tumor cell migration and invasion properties by transwell assays. The effect of siRNA PCGEM1 and miR-145 transfection on prostate cancer growth in vivo was examined in the (nu/nu) mouse model. PCGEM1 and miR-145 exhibited reciprocal regulation; downregulation of PCGEM1 expression in LNCaP cells increased expression of miR-145, while overexpression of miR-145 decreased PCGEM1 expression. Transfection of the miR-145 expression vector and siRNA PCGEM1 inhibited tumor cell proliferation, migration, and invasion, and induced early apoptosis both in vitro. In contrast, there was no effect on RWPE-1 cells. We demonstrate a reciprocal negative control relationship between PCGEM1 and miR-145 that regulates both LNCaP cell proliferation and nu/nu PCa tumor growth. The results also identify PCGEM1 and associated regulators as possible targets for PCa therapy.

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Advances in understanding chromosome silencing by the long non-coding RNA Xist

Cited by 55 publications

References 88 publications

RNA as a fundamental component of interphase chromosomes: could repeats prove key?

RNA as a fundamental component of interphase chromosomes: could repeats prove key?

Efficient in vivo deletion of a large imprinted lncRNA by CRISPR/Cas9

Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells

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