2. Academic Validation
  3. Phosphorylation-dependent charge blocks regulate the relaxation of nuclear speckle networks

Phosphorylation-dependent charge blocks regulate the relaxation of nuclear speckle networks

  • Mol Cell. 2025 May 1;85(9):1760-1774.e7. doi: 10.1016/j.molcel.2025.03.016.
Mengjun Zhang 1,  Zhuang Gu 1,  Yingtian Sun 1,  Yichen Dong 1,  Junlin Chen 2,  Li Shu 3,  Suibin Ma 1,  Jierui Guo 1,  Yuhang Liang 4,  Qingming Qu 1,  Ning Fang 4,  Chuan-Qi Zhong 1,  Yifan Ge 3,  Zhongwen Chen 3,  Shaohui Huang 5,  Xin Zhang 2,  Bo Wang 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
  • 2 School of Life Sciences and Research Center for Industries of the Future, Westlake University, Hangzhou 310030, China.
  • 3 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 203201, China.
  • 4 The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
  • 5 School of Biological Sciences, University of Chinese Academy of Sciences, Beijing 101408, China.
  • 6 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China. Electronic address: bowang@xmu.edu.cn.
PMID: 40233760 DOI: 10.1016/j.molcel.2025.03.016
Abstract

Nuclear speckles (NSs) are viscoelastic network fluids formed via phase separation coupled to percolation (PSCP). Intermolecular crosslinks of SRRM2 lead to the emergence of system-spanning networks, although the physicochemical grammar governing SRRM2 PSCP remains poorly decoded. Here, we demonstrate that SRRM2 is extensively phosphorylated within the intrinsically disordered region (IDR), creating alternating charge blocks. We show that this specific charge pattern does not markedly alter the condensation threshold of SRRM2 in cells. Instead, SRRM2 charge blocks intensify intra-network molecular interactions to modulate the material properties of mesoscopic SRRM2 condensates. We further identify Casein Kinase 2 (CK2) as the upstream enzyme to catalyze SRRM2 phosphorylation. Phosphorylation of SRRM2 IDR by CK2 facilitates NS relaxation, which is associated with enhanced efficiency of mRNA splicing to safeguard genome stability during DNA damage. Our findings reveal important regulatory mechanisms of charge blocks in modulating the material properties and functions of biomolecular condensates in human cells.

Keywords

CK2; SRRM2; alternative splicing; charge blocks; coarsening; elastic bending rigidity; interfacial tension; nuclear speckles; phase separation; phosphorylation.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z