A circular RNA-gawky-chromatin regulatory axis modulates stress-induced transcription

作者全名："Su, Rui; Zhou, Min; Lin, Jiamei; Shan, Ge; Huang, Chuan"

作者地址："[Su, Rui; Lin, Jiamei; Huang, Chuan] Chongqing Univ, Sch Life Sci, Chongqing 401331, Peoples R China; [Zhou, Min] Chongqing Med Univ, Dept Obstet & Gynecol, Women & Childrens Hosp, Chongqing 401147, Peoples R China; [Zhou, Min] Chongqing Hlth Ctr Women & Children, Dept Obstet & Gynecol, Chongqing 401147, Peoples R China; [Shan, Ge] Univ Sci & Technol China, Sch Basic Med Sci, Div Life Sci & Med, Hefei 230027, Peoples R China"

通信作者："Huang, C (通讯作者)，Chongqing Univ, Sch Life Sci, Chongqing 401331, Peoples R China."

来源：NUCLEIC ACIDS RESEARCH

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001177991800001

JCR分区：Q1

影响因子：16.6

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

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摘要："In response to heavy metal stress, the RNA-binding protein (RBP) gawky translocates into the nucleus and acts as a chromatin-interacting factor to activate the transcription of many stress-responsive genes. However, the upstream regulators of gawky-mediated transcription and their mechanistic details remain unknown. Here, we identified a class of metal-responsive element-containing circRNAs (MRE circRNAs) which specifically interact with gawky during copper stress. Using classic stress-responsive genes as a readout (Drosophila MT), we found that overexpression of MRE circRNAs led to a significant repression in stress-induced transcription. Mechanistically, MRE circRNAs promote the dissociation of gawky from chromatin and increase its aberrant cytoplasmic accumulation, which ultimately impedes the loading of RNA polymerase II to the active gene loci. The MRE motif serves as an important RNA regulon for maintaining the circRNA-gawky interaction, loss of which impaired the inhibitory effects of MRE circRNAs on gawky. Through RNA-seq analyses, we then identified over 500 additional stress-responsive genes whose induced transcription was attenuated upon MRE circRNA overexpression. Finally, we uncovered the physiological relevance of MRE circRNA-mediated regulation in cellular defense against copper overloading. Taken together, this study proposes that the circRNA-RBP-chromatin axis may represent a fundamental regulatory network for gene expression in eukaryotic cells. Graphical Abstract"

基金机构："National Natural Science Foundation of China [32270601, 32070633]; Chongqing Talents Plan for Young Talents [cstc2022ycjh-bgzxm0140]; Fundamental Research Funds for the Central Universities of China [2023CDJXY-009]; Innovation Support Program for Overseas Returned Scholars of Chongqing, China [cx2019142]; National Natural Science Foundation of China [32070633]"

基金资助正文："National Natural Science Foundation of China [32270601, 32070633]; Chongqing Talents Plan for Young Talents [cstc2022ycjh-bgzxm0140]; Fundamental Research Funds for the Central Universities of China [2023CDJXY-009]; Innovation Support Program for Overseas Returned Scholars of Chongqing, China [cx2019142]. Funding for open access charge: National Natural Science Foundation of China [32070633]."