PXD064175

PXD064175 is an original dataset announced via ProteomeXchange.

Title	HSPA1A and DNAJB1 regulate NELF condensate reversibility to safeguard transcriptional recovery under heat stress
Description	The negative elongation factor (NELF) is essential in establishing RNA Polymerase II (Pol II) pausing at promoter-proximal regions, providing a key regulatory checkpoint for precise gene expression control. In response to heat shock (HS) stress, NELF has been observed to form nuclear condensates, but the mechanisms that govern their dynamic behavior and functional significance during stress adaptation remain poorly understood. Here, we leverage a nanobody-based proximity labeling (NbPro) strategy to characterize the composition and regulation of HS-induced NELF condensates. Through this approach, we identify molecular chaperones HSPA1A and DNAJB1 as key regulators that maintain the dynamic reversibility of NELF condensates. While dispensable for HS-induced transcriptional downregulation, this process is essential for transcriptional restart during recovery. Mechanistically, DNAJB1 recognizes NELFA and facilitates the recruitment of HSPA1A into NELF condensates. This coordinated action prevents NELF condensates from transitioning into aggregates and ensures their reversible disassembly during recovery. We further show that NELFA undergoes a tightly regulated phosphorylation-dephosphorylation cycle during HS. Disruption of NELF condensate dynamics leads to sustained NELFA phosphorylation, reduced chromatin binding, impaired Pol II pausing, and the release of non-productive Pol II complexes, ultimately compromising transcriptional recovery. Collectively, our findings reveal a critical chaperone-dependent mechanism that governs NELF condensate dynamics and highlight promoter-proximal pausing not merely as a means of transcriptional repression, but as a checkpoint to prevent immature Pol II escape and ensure productive transcriptional restart following heat shock.
HostingRepository	iProX
AnnounceDate	2025-05-21
AnnouncementXML	Submission_2026-03-04_00:51:16.599.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuyao Jiang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-21 18:35:00	ID requested
⏵ 1	2026-03-04 00:51:17	announced

Jiang S, Jia Z, Zhu W, Liu Y, Fu H, Zhu F, Li Z, Yang J, Zhu Y, Sun Z, Zhu T, Quan X, Jiao H, Huang K, Wu Z, Zou W, Yang B, Lu Y, Zhang L, Zhou F, Fang D, Lu H, HSPA1A and DNAJB1 regulate NELF condensate dynamics to safeguard transcriptional recovery under heat stress. Mol Cell, 86(4):674-692.e10(2026) [pubmed]

submitter keyword: PL-MS

Huasong Lu
contact affiliation	Zhejiang University
contact email	huasong_lu@zju.edu.cn
lab head
Shuyao Jiang
contact affiliation	Zhejiang University
contact email	jiang_sy@zju.edu.cn
dataset submitter

iProX dataset URI