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Long noncoding RNAs in mammalian cells: what, where, and why?

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Abstract Not all long, polyadenylated cellular RNAs encode polypeptides. In recent years, it has become apparent that a number of organisms express abundant amounts of transcripts that lack open reading frames or that are retained in the nucleus. Rather than accumulating silently in the cell, we now know that many of these long noncoding RNAs (lncRNAs) play important roles in nuclear architecture or in the regulation of gene expression. Here, we discuss some recent progress in our understanding of the functions of a number of important lncRNAs in mammalian cells. Copyright © 2010 John Wiley & Sons, Ltd. This article is categorized under: RNA Processing > RNA Editing and Modification Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Development

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A schematic overview of a number of known or suspected functions of long noncoding RNAs in mammalian cells. See text for details.

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Long noncoding RNAs in nuclear subcompartments. Human nuclear‐enriched abundant transcript 2 (NEAT2) [also known as metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in mouse] localizes to nuclear speckles but is not required for their structural integrity. See text for details. Nascent MALAT1 transcripts can be processed by an unusual mechanism of RNase P cleavage to generate the 5 end of mascRNA (MALAT1‐associated small cytoplasmic RNA) and the 3 end of the mature MALAT1 transcripts, which localize to nuclear speckles.

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Long noncoding RNA‐mediated transcription regulation by enhancer competition. The H19 lncRNA is transcribed only maternally from the imprinted H19/Igf2 locus, which is controlled by chromatin insulators that lie upstream of the H19 gene. On the maternal chromosome, the insulator sequence is unmethylated and binds CCCTC‐binding factor (CTCF), and thus prevents the enhancers from interacting with the Igf2 promoter, but instead activates H19 gene transcription. On the paternal chromosome, insulators are methylated and do not bind CTCF, thus allowing the enhancers to activate Igf2 transcription.

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An example of long noncoding RNA (lncRNA)‐mediated transcription activation. An ultraconserved enhancer region from the Dlx5/6 locus is transcribed to generate an lncRNA, Evf‐2, which forms a stable complex with a homeodomain protein Dlx‐2. Binding of Evf‐2 activates Dlx‐2 as a transcriptional enhancer for Dlx5/6.

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An example of long noncoding RNA (lncRNA)‐mediated transcription suppression. In quiescent cells, lncRNA transcribed from the upstream of the minor promoter of DHFR gene forms a triplex with the transcriptional factor IIB and the major promoter. This triplex leads to the dissociation of the preinitiation complex from the major promoter, which subsequently inhibits its transcription.

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Long noncoding RNA (lncRNA)‐mediated transcription suppression following DNA damage. In response to DNA damage, lncRNAs are transcribed from the 5‐upstream region of the CCND1 gene and recruit the RNA‐binding protein translocated in liposarcoma, which modulates CREB‐binding protein and p300 to inhibit CCND1 transcription.

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Long noncoding RNA (lncRNA)‐mediated heterochromatin silencing. Some lncRNAs that are transcribed by RNA polymerase II recruit transcriptional repressive complexes to silence specific genomic regions, both in cis and in trans. Examples shown here are Air, Kcnq1ot1, Xist/RepA, HOTAIR. See text for details.

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Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs
RNA Processing > RNA Editing and Modification
RNA in Disease and Development > RNA in Development

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