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The widely expressed fusion protein CTBS-GNG5 regulates cell cycle progression by stabilizing IGF2BP2

This article is a preprint and has not been certified by peer review.

Authors

    Liang Cheng,  
    Liang Cheng
    • Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    Jingtong Zhang,   Xiaole Lu,   Chenwei Yang,   Fujun Qin,   Yuhang Huang,   Ming Huang,   Junlin Lu,   Sarah Lynch,   Justin Elfman,   Ruihui Xie,   Shengmeng Peng,   Siting Chen,   Baoqing He,   Haifeng Wang,   Tianxin Lin,   Hui Li,   Jian Huang,   Xu Chen
    Xu Chen
    • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Categories
Cell Biology
Keywords
Chimeric RNA; Fusion Protein; Cell Cycle; mRNA Stability; IGF2BP2; Ubiquitination; housekeeping protein

Abstract

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.

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DOI:

https://doi.org/10.65215/LTSpreprints.2026.02.19.000133

Submission ID:

133

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Posted

2026-02-19

How to Cite

Cheng, L., Zhang, J., Lu, X., Yang, C., Qin, F., Huang, Y., Huang, M., Lu, J., Lynch, S., Elfman, J., Xie, R., Peng, S., Chen, S., He, B., Wang, H., Lin, T., Li, H., Huang, J., & Chen, X. (2026). The widely expressed fusion protein CTBS-GNG5 regulates cell cycle progression by stabilizing IGF2BP2. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.02.19.000133

Declaration of Competing Interests

The authors declare no competing interests to disclose.

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The copyright holder for this preprint is the author/funder.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.