The widely expressed fusion protein CTBS-GNG5 regulates cell cycle progression by stabilizing IGF2BP2
摘要
Chimeric RNAs are increasingly recognized as important regulatory molecules, yet their roles in fundamental cellular processes within normal physiology remain largely unexplored. Here, we identify CTBS-GNG5, a ubiquitously expressed chimeric RNA, which exhibits housekeeping-gene-like expression patterns across diverse normal and malignant tissues. Furthermore, we developed a highly specific monoclonal antibody targeting the unique junction of the CTBS-GNG5 fusion protein and have confirmed its widespread protein expression across tissues of various origin. We demonstrate that the CTBS-GNG5-encoded fusion protein promotes cell cycle progression and proliferation both in vitro and in vivo. The fusion protein directly binds and stabilizes the m6A reader IGF2BP2, attenuating its degradation by the ubiquitin-mediated proteasome. The stabilization of IGF2BP2 enhances the mRNA stability of key cell cycle regulators, including CDK1, TOP2A, and CDCA2, thereby driving G1/S phase transition. Our findings unveil a paradigm-shifting role for a ubiquitous chimeric RNA as a central regulator of the cell cycle, bridging normal cellular homeostasis and oncogenic proliferation.
指标
DOI：
Submission ID：
下载次数
已发布
如何引用
利益冲突声明
作者声明无任何需要披露的利益冲突。
Copyright
本预印本的版权持有者为作者/资助方。
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.