Stress-induced nuclear condensation of NELF drives transcriptional downregulation
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/134062 |
| _version_ | 1826217564059992064 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rawat, Prashant |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:05:40Z |
| format | Article |
| id | mit-1721.1/134062 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:05:40Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1340622021-10-28T03:02:32Z Stress-induced nuclear condensation of NELF drives transcriptional downregulation 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 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. 2021-10-27T19:57:53Z 2021-10-27T19:57:53Z 2021 2021-08-03T17:32:35Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134062 en 10.1016/j.molcel.2021.01.016 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | 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 Stress-induced nuclear condensation of NELF drives transcriptional downregulation |
| title | Stress-induced nuclear condensation of NELF drives transcriptional downregulation |
| title_full | Stress-induced nuclear condensation of NELF drives transcriptional downregulation |
| title_fullStr | Stress-induced nuclear condensation of NELF drives transcriptional downregulation |
| title_full_unstemmed | Stress-induced nuclear condensation of NELF drives transcriptional downregulation |
| title_short | Stress-induced nuclear condensation of NELF drives transcriptional downregulation |
| title_sort | stress induced nuclear condensation of nelf drives transcriptional downregulation |
| url | https://hdl.handle.net/1721.1/134062 |
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