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

Permanent link
https://hdl.handle.net/10037/15610
DOI
https://doi.org/10.1074/jbc.RA118.004473
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Date
2018-10-10
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Lellahi, Seyed Mohammad; Rosenlund, Ingrid Arctander; Hedberg, Annica; Kiær, Liv Torill; Mikkola, Ingvild; Knutsen, Erik; Perander, Maria
Abstract
The long noncoding RNA (lncRNA) NEAT1 (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. NEAT1 and paraspeckle formation are increased in cells upon exposure to a variety of environmental stressors and believed to play an important role in cell survival. The present study was undertaken to further investigate the role of NEAT1 in cellular stress response pathways. We show that NEAT1 is a novel target gene of heat shock transcription factor 1 (HSF1) and is up-regulated when the heat shock response pathway is activated by sulforaphane (SFN) or elevated temperature. HSF1 binds specifically to a newly identified conserved heat shock element in the NEAT1 promoter. In line with this, SFN induced the formation of NEAT1-containing paraspeckles via an HSF1-dependent mechanism. HSF1 plays a key role in the cellular response to proteotoxic stress by promoting the expression of a series of genes, including those encoding molecular chaperones. We have found that the expression of HSP70, HSP90, and HSP27 is amplified and sustained during heat shock in NEAT1-depleted cells compared with control cells, indicating that NEAT1 feeds back via an unknown mechanism to regulate HSF1 activity. This interrelationship is potentially significant in human diseases such as cancer and neurodegenerative disorders.
Description
This research was originally published in the Journal of Biological Chemistry, 293(49), 18965–18976. © the American Society for Biochemistry and Molecular Biology or © the Author(s). Terms and conditions apply.
Is part of
Lellahi, S.M. (2019). Breast cancer-associated NEAT1 in cellular stress response pathways. (Doctoral thesis). https://hdl.handle.net/10037/15809.
Publisher
American Society for Biochemistry and Molecular Biology
Citation
Lellahi, S.M., Rosenlund, I.A., Hedberg, A., Kiær, L.T., Mikkola, I., Knutsen, E. & Perander, M. (2018). The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response. Journal of Biological Chemistry, 293(49), 18965–18976. https://doi.org/10.1074/jbc.RA118.004473
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