<i>MEN ε/β</i> nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles

Sunwoo, Hongjae; Dinger, Marcel E.; Wilusz, Jeremy E.; Amaral, Paulo; Mattick, John S.; Spector, David L.

doi:10.1101/gr.087775.108

Cited by 600 publications

(693 citation statements)

References 50 publications

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“…There may be classes of lincRNAs that function in entirely different ways. For example, the lincRNAs NEAT1 and NEAT2 have been recently shown to be important in the formation of paraspeckles (25), and the lincRNA NRON has a role in repressing nuclear import (26). It is possible that additional lincRNAs have roles in these and numerous other cellular pathways.…”

Section: Discussionmentioning

confidence: 99%

Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression

Khalil

Guttman

Huarte

et al. 2009

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

2,675

2,427

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We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, we expand the catalog of human lincRNAs to Ϸ3,300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR binds the polycomb repressive complex (PRC)2, we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that Ϸ20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Also, we show that siRNAmediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression, and that the up-regulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression.histone modifications ͉ epigenetic regulation ͉ polycomb

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Section: Discussionmentioning

confidence: 99%

Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression

Khalil

Guttman

Huarte

et al. 2009

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

2,675

2,427

View full text Add to dashboard Cite

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“…Importantly, no floating cells (dead cells) were seen by depletion of NR_015389, AK091718, and AK055657 under microscopic observation (data not shown), suggesting that these SLiTs are modifying factors but are not essential for cell proliferation. Biochemical fractionation indicated that NR_015389, AK091718, AK055657, AK123363, and NR_033895 were predominantly enriched in the heavy fractions of the sucrose density-gradient analysis, along with nuclear lncRNAs, such as NEAT1 (Clemson et al 2009;Sasaki et al 2009;Sunwoo et al 2009) and MALAT1, which are components of nuclear bodies ( Fig. 5B; Supplemental Fig.…”

Section: Bric-seq Reveals Hundreds Of Slits In Mammalsmentioning

confidence: 99%

Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals

Tani¹,

Mizutani²,

Salam³

et al. 2012

Genome Res.

398

422

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Mammalian genomes produce huge numbers of noncoding RNAs (ncRNAs). However, the functions of most ncRNAs are unclear, and novel techniques that can distinguish functional ncRNAs are needed. Studies of mRNAs have revealed that the half-life of each mRNA is closely related to its physiological function, raising the possibility that the RNA stability of an ncRNA reflects its function. In this study, we first determined the half-lives of 11,052 mRNAs and 1418 ncRNAs in HeLa Tet-off (TO) cells by developing a novel genome-wide method, which we named 59-bromo-uridine immunoprecipitation chase-deep sequencing analysis (BRIC-seq). This method involved pulse-labeling endogenous RNAs with 59-bromo-uridine and measuring the ongoing decrease in RNA levels over time using multifaceted deep sequencing. By analyzing the relationship between RNA half-lives and functional categories, we found that RNAs with a long half-life (t 1/2 $ 4 h) contained a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short halflife (t 1/2 < 4 h) included known regulatory ncRNAs and regulatory mRNAs. The stabilities of a significant set of short-lived ncRNAs are regulated by external stimuli, such as retinoic acid treatment. In particular, we identified and characterized several novel long ncRNAs involved in cell proliferation from the group of short-lived ncRNAs. We designated this novel class of ncRNAs with a short half-life as Short-Lived noncoding Transcripts (SLiTs). We propose that the strategy of monitoring RNA half-life will provide a powerful tool for investigating hitherto functionally uncharacterized regulatory RNAs.

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“…A similar mechanism has been reported for two tRNA-like molecules generated from the mammalian lncRNAs MALAT1 and Menβ . In both cases, RNase P recognizes the tRNA-like structure in a nascent RNAPII transcript and cleaves it to simultaneously generate the 3′-end of the mature nuclear-retained lncRNA and the 5′-end of the tRNA-like small RNA [31, 32]. Recently, 132 genomic loci resembling the MALAT1 3′-end processing module have been identified among several vertebrate genomes [33].…”

Section: Discussionmentioning

confidence: 99%

A stable tRNA-like molecule is generated from the long noncoding RNA GUT15 in Arabidopsis

et al. 2018

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The Arabidopsis GUT15 RNA belongs to a class of noncoding RNAs that are expressed from the intergenic regions of protein-coding genes. We show that the RNA polymerase II transcribed GUT15 transcript serves as a precursor for two stable RNA species, a tRNA-like molecule and GUT15-tRF-F5, which are both encoded by the final intron in the GUT15 gene. The GUT15-encoded tRNA-like molecule cannot be autonomously transcribed by RNA polymerase III. However, this molecule contains a CCA motif, suggesting that it may enter the tRNA maturation pathway. The GUT15-encoded tRNA-like sequence has an inhibiting effect on the splicing of its host intron. Moreover, we demonstrate that the canonical tRNA genes nested within introns do not affect the splicing patterns of their host protein-coding transcripts.

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MEN ε/β nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles

Cited by 600 publications

References 50 publications

Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression

Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression

Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals

A stable tRNA-like molecule is generated from the long noncoding RNA GUT15 in Arabidopsis

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