NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies

Hirose, Tetsuro; Virnicchi, Giorgio; Tanigawa, Akie; Naganuma, Takao; Li, Ruohan; Kimurâ, Hiroshi; Yokoi, Takeshi; Nakagawa, Shinichi; Bénard, Marianne; Fox, Archa H.; Pierron, Gérard

doi:10.1091/mbc.e13-09-0558

Cited by 407 publications

(466 citation statements)

References 36 publications

(65 reference statements)

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“…This patchy pattern of localization, which was not observed for the other PSPs (Fig. S1C), was even more evident in enlarged paraspeckles generated by treatment with the proteasome inhibitor MG132 (9) (Fig. 1D, Upper Right).…”

Section: Resultsmentioning

confidence: 70%

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SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies

Kawaguchi

Tanigawa²,

Naganuma

et al. 2015

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

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Paraspeckles are subnuclear structures that form around nuclear paraspeckle assembly transcript 1 (NEAT1) long noncoding RNA (lncRNA). Recently, paraspeckles were shown to be functional nuclear bodies involved in stress responses and the development of specific organs. Paraspeckle formation is initiated by transcription of the NEAT1 chromosomal locus and proceeds in conjunction with NEAT1 lncRNA biogenesis and a subsequent assembly step involving >40 paraspeckle proteins (PSPs). In this study, subunits of SWItch/Sucrose NonFermentable (SWI/SNF) chromatin-remodeling complexes were identified as paraspeckle components that interact with PSPs and NEAT1 lncRNA. EM observations revealed that SWI/SNF complexes were enriched in paraspeckle subdomains depleted of chromatin. Knockdown of SWI/SNF components resulted in paraspeckle disintegration, but mutation of the ATPase domain of the catalytic subunit BRG1 did not affect paraspeckle integrity, indicating that the essential role of SWI/SNF complexes in paraspeckle formation does not require their canonical activity. Knockdown of SWI/SNF complexes barely affected the levels of known essential paraspeckle components, but markedly diminished the interactions between essential PSPs, suggesting that SWI/SNF complexes facilitate organization of the PSP interaction network required for intact paraspeckle assembly. The interactions between SWI/SNF components and essential PSPs were maintained in NEAT1-depleted cells, suggesting that SWI/SNF complexes not only facilitate interactions between PSPs, but also recruit PSPs during paraspeckle assembly. SWI/SNF complexes were also required for Satellite III lncRNA-dependent formation of nuclear stress bodies under heat-shock conditions. Our data suggest the existence of a common mechanism underlying the formation of lncRNA-dependent nuclear body architectures in mammalian cells.chromatin-remodeling complex | long noncoding RNA | nuclear bodies | ribonucleoprotein assembly

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Section: Resultsmentioning

confidence: 70%

“…Paraspeckles are ∼360 nm in diameter (8); hence, they are considered huge among RNP particles. Paraspeckles regulate the expression of a number of genes via the sequestration of specific proteins and RNAs (4,9,10), and are physiologically involved in the development of the corpus luteum and the mammary gland in mice (11,12).…”

mentioning

confidence: 99%

SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies

Kawaguchi

Tanigawa²,

Naganuma

et al. 2015

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

Self Cite

140

126

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“…Recently, NEAT1 was found to repress the transcription of some genes by protein sequestration into paraspeckles (22). Here, we discovered that NEAT1 might function by another potential molecular mechanism in NSCLC progression-acting as 'molecular sponges' to regulate microRNAs.…”

Section: Discussionmentioning

confidence: 96%

Long non-coding RNA NEAT1 regulates E2F3 expression by competitively binding to miR-377 in non-small cell lung cancer

Zhang

Dong

et al. 2017

Oncology Letters

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Abstract.It has previously been demonstrated that the long non-coding RNA (lncRNA) nuclear enriched abundant transcript (NEAT)-1 is increased in multiple cancers and may be associated with cancer development. However, the function and mechanism of NEAT1 in non-small cell lung cancer (NSCLC) has not yet been fully elucidated. In the present study, the expression of NEAT1 in NSCLC was detected using quantitative polymerase chain reaction and association with survival was estimated. The effect of NEAT1 on proliferation was detected by growth curve and cell cycle analysis. Bioinformatics analysis was used to identify miRNAs that interact with NEAT1. Following this, a series of molecular biological techniques were used to verify the mechanism of NEAT1. The results indicated that NEAT1 was highly expressed in NSCLC, and high NEAT1 expression was associated with a shorter overall survival. NEAT1 promoted NSCLC cell growth and affected the cell cycle process in vitro. Furthermore, NEAT1 was observed to bind hsa-miR-377-3p, functioning as a competing endogenous RNA, which resulted in de-repression of its target gene E2F transcription factor 3 (E2F3). E2F3, as an oncogene, may promote NSCLC progression. These results suggested that NEAT1 may promote the development of NSCLC through the miR-377-3p-E2F3 pathway.

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“…At the molecular level, NEAT1 is important for the formation of paraspeckles, a type of mammalian nuclear RNA-protein body found in close proximity to nuclear speckles (Fox et al 2002;Hutchinson et al 2007). Paraspeckles modulate gene expression by sequestrating mRNAs and transcription factors (TFs) (Prasanth et al 2005;Chen and Carmichael 2009;Naganuma et al 2012;Choudhry et al 2014;Hirose et al 2014;Imamura et al 2014;West et al 2016), and their formation occurs when specific architectural proteins, including those of the DBHS (Drosophila behavior/human splicing) family, bind to nascent NEAT1 transcripts (Mao et al 2011). Many other protein and RNA factors localize to paraspeckles, some with potential roles in paraspeckle function and others not required for function but potentially regulated by paraspeckle sequestration (Prasanth et al 2005;Chen and Carmichael 2009;Naganuma et al 2012;Choudhry et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles

Harvey

Hodgetts

et al. 2017

RNA

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Large numbers of long noncoding RNAs have been discovered in recent years, but only a few have been characterized. NEAT1 (nuclear paraspeckle assembly transcript 1) is a mammalian long noncoding RNA that is important for the reproductive physiology of mice, cancer development, and the formation of subnuclear bodies termed paraspeckles. The two major isoforms of NEAT1 (3.7 kb NEAT1_1 and 23 kb NEAT1_2 in human) are generated from a common promoter and are produced through the use of alternative transcription termination sites. This gene structure has made the functional relationship between the two isoforms difficult to dissect. Here we used CRISPR-Cas9 genome editing to create several different cell lines: total NEAT1 knockout cells, cells that only express the short form NEAT1_1, and cells with twofold more NEAT1_2. Using these reagents, we obtained evidence that NEAT1_1 is not a major component of paraspeckles. In addition, our data suggest NEAT1_1 localizes in numerous nonparaspeckle foci we termed "microspeckles," which may carry paraspeckle-independent functions. This study highlights the complexity of lncRNA and showcases how genome editing tools are useful in dissecting the structural and functional roles of overlapping transcripts.

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NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies

Cited by 407 publications

References 36 publications

SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies

SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies

Long non-coding RNA NEAT1 regulates E2F3 expression by competitively binding to miR-377 in non-small cell lung cancer

Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles

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