An Architectural Role for a Nuclear Non-coding RNA: NEAT1 RNA is Essential for the Structure of Paraspeckles

By C. Clemson, John N. Hutchinson, S. Sara, Alexander W. Ensminger, A. Fox, A. Chess, J. Lawrence. Molecules and Cells, 2009

1,391 citations recorded by the source corpus.

Summary NEAT1 RNA, a highly abundant 4 kb ncRNA, is retained in nuclei in ~10–20 large foci that we show is completely coincident with paraspeckles, nuclear domains implicated in mRNA nuclear retention. Depletion of NEAT1 RNA via RNAi eradicates paraspeckles, suggesting it controls sequestration of the paraspeckle proteins, PSP1 and p54, factors linked to A-I editing. Unlike over-expression of PSP1, NEAT1 over-expression increases paraspeckle number, and paraspeckles emanate exclusively from the NEAT1 transcription site. The PSP-1 RNA binding domain is required for its co-localization with NEAT1 RNA in paraspeckles, and biochemical analyses supports that NEAT1 RNA binds with paraspeckle proteins. Unlike other nuclear retained RNAs, NEAT1 RNA is not A-I edited, consistent with a structural role in paraspeckles. Collectively results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/165fa3562428ff11de83abec58e4d3b77047241b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

The Genetic Signatures of Noncoding RNAs (2009, background): “Specific subcellular localization [19–22,52,56]”
Non‐coding RNAs: regulators of disease (2010, background): “For instance, the NRON lncRNA is involved in the cytoplasmic-to-nuclear shuttling of the NFAT transcription factor [123], and the lncRNA NEAT1 /MEN ε/β is required for the formation of the nuclear subcompartment paraspeckles in differentiated cells and regulates the movement of primate-specific mRNA”
Characterising the RNA targets and position-dependent splicing regulation by TDP-43; implications for neurodegenerative diseases (2011, background): “Whereas NEAT1 was previously identified as a 4-kb ncRN”
The Nuclear-Retained Noncoding RNA MALAT1 Regulates Alternative Splicing by Modulating SR Splicing Factor Phosphorylation (2010, background): “Our results imply that MALAT1 is not a structural RNA, similar to what has been suggested earlier (Clemson et al., 2009), but that it modulates the speckle association of a subset of pre-mRNA splicing factors.”
Long noncoding RNAs: Cellular address codes in development and disease (2013, positive): “Upon transcription of NEAT1, diffusible components of this domain nucleate at the site of NEAT1 accumulation, leading to the formation of the Paraspeckle (Figure 3A) (Chen and Carmichael, 2009; Clemson et al., 2009; Mao et al., 2011; Sasaki et al., 2009; Shevtsov and Dundr, 2011; Sunwoo et al., 2009”
Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes (2011, background): “We saw specific start sites marked by harringtonine followed by ribosome footprints extending to the first in-frame stop codon (Figures 5B–5D) (Clemson et al., 2009).”
lincRNAs: Genomics, Evolution, and Mechanisms (2013, positive): “For example, Neat1/Menb and Malat1 bind multiple proteins localizing to the paraspeckles and nuclear speckles, respectively, and Menb is essential for paraspeckle formation (Clemson et al., 2009; Sunwoo et al., 2009; Murthy and Rangarajan, 2010; Souquere et al., 2010; Tripathi et al., 2010).”
Linking Long Noncoding RNA Localization and Function. (2016, background): “1, are abundant lncRNAs that are localized to paraspeckles [30].”