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ZMAT2 condensates regulate the alternative splicing of TRIM28 to reduce cellular ROS accumulation, thereby promoting the proliferation of HCC cells

Authors :
Yaning Zhu
Jiong Li
Sang Li
Zhe Yang
Zhengkang Qiao
Xingshi Gu
Zhenhu He
Di Wu
Xiaoqian Ma
Shanhu Yao
Cejun Yang
Min Yang
Lu Cao
Juan Zhang
Wei Wang
Pengfei Rong
Source :
Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-18 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

Details

Language :
English
ISSN :
1478811X
Volume :
22
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cell Communication and Signaling
Publication Type :
Academic Journal
Accession number :
edsdoj.f26cc0bf3f0b4b27b10922f0636faaa5
Document Type :
article
Full Text :
https://doi.org/10.1186/s12964-024-01790-9