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GLTSCR1 coordinates alternative splicing and transcription elongation of ZO1 to regulate colorectal cancer progression
Fengyan Han1,† , Beibei Yang1,† , Mingyue Zhou2,† , Qiong Huang1,3,4 , Minglang Mai1 , Zhaohui Huang2 , Maode Lai3,4,5 , Enping Xu1,3,4,* , Honghe Zhang1,3,4,*
1Department of Pathology and Women’s Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China
2Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China
3Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University, Hangzhou 310058, China
4Cancer Center, Zhejiang University, Hangzhou 310058, China
5Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China
†These authors contributed equally to this work.
*Correspondence to:Enping Xu , Email:xep@zju.edu.cn Honghe Zhang , Email:honghezhang@zju.edu.cn
J Mol Cell Biol, Volume 14, Issue 2, February 2022, mjac009,  https://doi.org/10.1093/jmcb/mjac009
Keyword: colorectal cancer, alternative splicing, transcription elongation, GLTSCR1

Alternative splicing (AS) and transcription elongation are vital biological processes, and their dysregulation causes multiple diseases, including tumors. However, the coregulatory mechanism of AS and transcription elongation in tumors remains unclear. This study demonstrates a novel AS pattern of tight junction protein 1 (ZO1) regulated by the RNA polymerase II elongation rate in colorectal cancer (CRC). Glioma tumor suppressor candidate region gene 1 (GLTSCR1) decreases the transcription elongation rate of ZO1 to provide a time window for binding of the splicing factor HuR to the specific motif in intron 22 of ZO1 and spliceosome recognition of the weak 3′ and 5′ splice sites in exon 23 to promote exon 23 inclusion. Since exon 23 inclusion in ZO1 suppresses migration and invasion of CRC cells, our findings suggest a novel potential therapeutic target for CRC.


Volume 14, Issue 2
February 2022