Stress-induced nuclear condensation of NELF drives transcriptional downregulation

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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Molecular cell. - 81, 5 (2021) , 1013-1026.e11, ISSN: 1097-4164

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2021
Urheber
Rawat, Prashant
Boehning, Marc
Hummel, Barbara
Aprile-Garcia, Fernando
Pandit, Anwit Shriniwas
Eisenhardt, Nathalie
Khavaran, Ashkan
Niskanen, Einari
Vos, Seychelle M.
Palvimo, Jorma J.
Pichler, Andrea
Cramer, Patrick
Sawarkar, Ritwick

DOI
10.1016/j.molcel.2021.01.016
URN
urn:nbn:de:bsz:25-freidok-1942108
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25.03.2025, 13:45 MEZ

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  • 2021

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