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Stress-induced nuclear condensation of NELF drives transcriptional downregulation
Name
1-s2.0-S1097276521000162-main.pdf
Description
Published version
Size
4.6 MB
Format
Adobe PDF
Checksum (MD5)
55d30b5777390a1dfc3c9a7b86dde564
Author(s)
Rawat, Prashant
Boehning, Marc
Hummel, Barbara
Aprile-Garcia, Fernando
Pandit, Anwit S
Eisenhardt, Nathalie
Khavaran, Ashkan
Niskanen, Einari
Vos, Seychelle M
Palvimo, Jorma J
Date Issued
2021
Journal
Molecular Cell
Publisher
Elsevier BV
Version
Final published version
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.
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
10.1016/j.molcel.2021.01.016
