A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains

By John N. Hutchinson, Alexander W. Ensminger, C. Clemson, Christopher R. Lynch, J. Lawrence, A. Chess. BMC Genomics, 2007

977 citations recorded by the source corpus.

BackgroundNoncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment.ResultsThis screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11: NEAT1, a noncoding RNA from the locus encoding for TncRNA, and NEAT2 (also known as MALAT-1). While the two NEAT transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs. NEAT2 is extraordinarily well conserved for a noncoding RNA, more so than even XIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, NEAT1 localizes to the periphery of such domains, whereas the neighboring transcript, NEAT2, is part of the long-sought polyadenylated component of nuclear speckles.ConclusionOur genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2. The function of these noncoding RNAs in mRNA metabolism is suggested by their high levels of conservation and their intimate association with SC35 splicing domains in multiple mammalian species.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dc5bf79bfb5b865d729b15512bad5d3f67d07d04

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Citations in the corpus

LNCcation: lncRNA localization and function (2021, background): “MALAT1, TERRA, and H19 were shown to be packaged in exosomes, and the lncRNA LASSIE stabilizes endothelial adherens junctions via association with PECAM-1.”
Linking Long Noncoding RNA Localization and Function. (2016, background): “First, MALAT1 and NEAT1_long are two lncRNAs that are localized to nuclear speckles [68] and paraspeckles [31], respectively.”
Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB (2013, background): “MALAT1 is a highly abundant nucleusrestricted RNA that localizes to nuclear speckles, a sub-nuclear domain suggested to coordinate RNA polymerase II transcription, pre-mRNA splicing and mRNA export [43,44,45].”
Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus (2018, background): “Because the U1 and Malat1 RNAs are known to localize at nuclear speckles (Hutchinson et al., 2007), a nuclear body that contains proteins involved in mRNA splicing and processing (Spector and Lamond, 2011), we hypothesized that inter-chromosomal interactions occurring between regions in the active…”
lincRNAs: Genomics, Evolution, and Mechanisms (2013, neutral): “, 2011) but misses some bona fide single-exon lincRNAs, such as Malat1 and Neat1 (Hutchinson et al., 2007).”
ncRNA- and Pc2 Methylation-Dependent Gene Relocation between Nuclear Structures Mediates Gene Activation Programs (2011, positive): “Interchromatin granule-specific localization of NEAT2 (Hutchinson et al., 2007) led us to examine the cellular localization of TUG1 by utilizing a molecular beacon targeting TUG1.”
Biogenesis and Function of Nuclear Bodies (2011, background): “Speckles have long been recognized to contain a population of poly(A)+ RNAs [68-70] and a recent report suggested that a lncRNA, Malat1, is part of these long-sought after poly(A)+ RNAs enriched in speckles [71].”
The Nuclear-Retained Noncoding RNA MALAT1 Regulates Alternative Splicing by Modulating SR Splicing Factor Phosphorylation (2010, background): “…1Aa0 and 1Ab0) (Manley and Krainer, 2010) in HeLa cells demonstrated enrich- 926 Molecular Cell 39, 925–938, September 24, 2010 ª2010 Elsevier ment of MALAT1 in nuclear speckles in interphase cells (Figures 1Aa–1Aa00 0), as also reported recently (Clemson et al., 2009; Hutchinson et al., 2007).”