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Stress-induced Nuclear Condensation of NELF Drives Transcriptional Downregulation
Prashant Rawat
Marc Boehning
Barbara Hummel
Fernando Aprile-Garcia
Anwit S. Pandit
Nathalie Eisenhardt
Ashkan Khavaran
Einari Niskanen
Seychelle M. Vos
Jorma J. Palvimo
Andrea Pichler
Patrick Cramer
Ritwick Sawarkar
出版
Universität
, 2021
URL
http://books.google.com.hk/books?id=Tv91zgEACAAJ&hl=&source=gbs_api
註釋
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