Stress-induced nuclear condensation of NELF drives transcriptional downregulation
2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Stress-induced nuclear condensation of NELF drives transcriptional downregulation
Rawat, P.; Boehning, M.; Hummel, B.; Aprile-Garcia, F.; Pandit, A. S.; Eisenhardt, N. & Khavaran, A. et al. (2021)
Molecular Cell, 81(5) pp. 1013.e11-1026.e11. DOI: https://doi.org/10.1016/j.molcel.2021.01.016
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Details
- Authors
- Rawat, Prashant; Boehning, Marc; Hummel, Barbara; Aprile-Garcia, Fernando; Pandit, Anwit S.; Eisenhardt, Nathalie; Khavaran, Ashkan; Niskanen, Einari; Vos, Seychelle M.; Palvimo, Jorma J.; Pichler, Andrea; Cramer, Patrick ; Sawarkar, Ritwick
- Abstract
- In response to stress, human cells coordinately downregulate transcription and translation of housekeeping genes. To downregulate transcription, the negative elongation factor (NELF) is recruited to gene promoters impairing RNA polymerase II elongation. Here we report that NELF rapidly forms nuclear condensates upon stress in human cells. Condensate formation requires NELF dephosphorylation and SUMOylation induced by stress. The intrinsically disordered region (IDR) in NELFA is necessary for nuclear NELF condensation and can be functionally replaced by the IDR of FUS or EWSR1 protein. We find that biomolecular condensation facilitates enhanced recruitment of NELF to promoters upon stress to drive transcriptional downregulation. Importantly, NELF condensation is required for cellular viability under stressful conditions. We propose that stress-induced NELF condensates reported here are nuclear counterparts of cytosolic stress granules. These two stress-inducible condensates may drive the coordinated downregulation of transcription and translation, likely forming a critical node of the stress survival strategy.
- Issue Date
- 2021
- Journal
- Molecular Cell
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Cramer
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Language
- English