期刊
MOLECULAR CELL
卷 82, 期 1, 页码 75-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2021.11.032
关键词
-
资金
- AIRC [23053]
- ERC-2019-SyG [855923 ASTRA]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [721890]
- PRIN 2017 [2017P352Z4, 2017FNZRN3]
- H2020 Program Sapienza Progetti Collaborativi''
The study reveals that circular RNA circZNF609 can directly interact with multiple mRNAs, increasing their stability and/or translation by recruiting the RNA-binding protein ELAVL1. The interaction with CKAP5 mRNA in particular regulates microtubule function and cell-cycle progression in cancer cells. Additionally, the downregulation of circZNF609 increases the sensitivity of cancer cell lines to different microtubule-targeting chemotherapeutic drugs.
Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据