The Hepatitis Delta Virus accumulation requires paraspeckle components and affects NEAT1 level and PSP1 localization

Beeharry, Yasnee; Goodrum, Gabrielle; Imperiale, Christian J.; Pelchat, Martin

doi:10.1038/s41598-018-24500-1

Cited by 26 publications

(30 citation statements)

References 69 publications

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“…Even though the function of NEAT1 is still not fully understood, several reports have suggested that increased NEAT1 expression regulates the expression of certain genes by sequestering specific mRNAs and proteins into paraspeckles (10 -12). NEAT1 expression is up-regulated in response to different cellular stresses, including viral infections, proteasome inhibition, oncogene-induced replication stress, and hypoxia (11)(12)(13)(14)(15)(16)(17). Emerging evidence suggests that NEAT1 plays a cytoprotective role, as cells deficient of NEAT1 display increased sensitivity toward stress-induced cell death (11,15).…”

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confidence: 99%

The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response

Lellahi¹,

Rosenlund²,

Hedberg³

et al. 2018

Journal of Biological Chemistry

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confidence: 99%

The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response

Lellahi¹,

Rosenlund²,

Hedberg³

et al. 2018

Journal of Biological Chemistry

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“…HDV RNA is known to associate with the pre-mRNA splicing factors p54nrb and PSF, which are the two core protein components of the mammalian paraspeckles 30 . The knockdown of p54nrb, PSF, or PSP1 paraspeckle proteins reduces HDV RNA genome accumulation 31 . Recent evidence links components of mammalian SWI/SNF complexes, namely BRG1 and BRM, to paraspeckle assembly without requiring their ATPase activity 32 .…”

Section: Discussionmentioning

confidence: 99%

Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication

et al. 2020

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Hepatitis Delta virus (HDV) is a satellite of Hepatitis B virus with a single-stranded circular RNA genome. HDV RNA genome synthesis is carried out in infected cells by cellular RNA polymerases with the assistance of the small hepatitis delta antigen (S-HDAg). Here we show that S-HDAg binds the bromodomain (BRD) adjacent to zinc finger domain 2B (BAZ2B) protein, a regulatory subunit of BAZ2B-associated remodeling factor (BRF) ISWI chromatin remodeling complexes. shRNA-mediated silencing of BAZ2B or its inactivation with the BAZ2B BRD inhibitor GSK2801 impairs HDV replication in HDV-infected human hepatocytes. S-HDAg contains a short linear interacting motif (SLiM) KacXXR, similar to the one recognized by BAZ2B BRD in histone H3. We found that the integrity of the S-HDAg SLiM sequence is required for S-HDAg interaction with BAZ2B BRD and for HDV RNA replication. Our results suggest that S-HDAg uses a histone mimicry strategy to co-activate the RNA polymerase II-dependent synthesis of HDV RNA and sustain HDV replication.

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“…Early analyses in mice indicated that whereas NEAT1_1 is ubiquitously expressed, the expression pattern of NEAT1_2, and thus the presence of paraspeckles, is more restricted 5 . Emerging evidence now suggests that NEAT1_2 and paraspeckles play critical roles in orchestrating specific gene expression upon cellular stress and at specific developmental stages [9][10][11][12][13][14][15][16][17][18] . Importantly, it was recently shown that the expression of NEAT1_2, but not total NEAT1, was associated with aggressive cancers 15 .…”

Section: Discussionmentioning

confidence: 99%

The expression of the long NEAT1_2 isoform is associated with human epidermal growth factor receptor 2-positive breast cancers

Knutsen

Lellahi

Aure

et al. 2020

Sci Rep

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The long non-coding RNA NEAT1 locus is transcribed into two overlapping isoforms, NEAT1_1 and NEAT1_2, of which the latter is essential for the assembly of nuclear paraspeckles. NEAT1 is abnormally expressed in a wide variety of human cancers. Emerging evidence suggests that the two isoforms have distinct functions in gene expression regulation, and recently it was shown that NEAT1_2, but not NEAT1_1, expression predicts poor clinical outcome in cancer. Here, we report that NEAT1_2 expression correlates with HER2-positive breast cancers and high-grade disease. We provide evidence that NEAT1_1 and NEAT1_2 have distinct expression pattern among different intrinsic breast cancer subtypes. Finally, we show that NEAT1_2 expression and paraspeckle formation increase upon lactation in humans, confirming what has previously been demonstrated in mice. The long non-coding RNA (lncRNA) NEAT1 (Nuclear Paraspeckle Assembly Transcript 1) has recently gained considerable attention as it is abnormally expressed in human diseases, including cancer and neurodegenerative disorders. The NEAT1 gene is transcribed into two isoforms, NEAT1_1 of 3.7 kb and NEAT1_2 of 22.3 kb, where NEAT1_1 completely overlaps with the 5′ end of NEAT1_2 1. NEAT1_2 is essential for the assembly of paraspeckles, dynamic nuclear ribonucleoprotein complexes that phase-separate from the nucleoplasm to form liquid drop-like structures 2-7. In contrast, NEAT1_1 expression is not sufficient to induce paraspeckle formation, and recent reports suggest that NEAT1_1 can localize to structures that are distinct from paraspeckles 7,8. NEAT1 expression and paraspeckle formation are upregulated in response to a variety of cellular stressors including mitochondrial stress, proteasome inhibition, oncogene-induced replication stress, hypoxia, heat shock, and viral infections 9-18. It is now generally accepted that NEAT1 and paraspeckles regulate gene expression at both transcriptional and post-transcriptional levels by acting as hubs that sequester specific gene regulatory proteins and mRNAs 16-20. Several lines of evidence suggest that NEAT1 and paraspeckles play critical roles in stress response pathways in general, and at specific developmental stages. NEAT1 knockout mice display compromised mammary gland development and corpus luteum formation 21,22. Moreover, it was recently shown that maternal and zygotic NEAT1-depletion frequently led to early developmental arrest at the 16-or 32-cell stage in mouse embryonic cells 23. Cancer cells are exposed to a variety of extrinsic and intrinsic stressors like hypoxia, proteotoxicity, DNA damage, and reactive metabolic intermediates 24. Such malignancy-associated stress has been shown to induce NEAT1 expression and paraspeckle formation in vivo 15,16. NEAT1 levels are elevated in hypoxic regions of breast cancer cell line xenografts, and skin tumors induced by genotoxic stress in mice, display increased NEAT1

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The Hepatitis Delta Virus accumulation requires paraspeckle components and affects NEAT1 level and PSP1 localization

Cited by 26 publications

References 69 publications

The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response

The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response

Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication

The expression of the long NEAT1_2 isoform is associated with human epidermal growth factor receptor 2-positive breast cancers

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