Exportin 4 depletion leads to nuclear accumulation of a subset of circular RNAs

Chen, Liang; Wang, Yucong; Lin, Jiamei; Song, Zhenxing; Wang, Qinwei; Zhao, Wenxia; Wang, Yan; Xiu, Xiaoyu; Deng, Yuqi; Li, Xiuzhi; Wang, Xiaolin; Li, Jingxin; Liu, Xu; Liu, Kunpeng; Zhou, Jincong; Li, Kuan; Liu, Yuchan; Liao, Shanhui; Deng, Qin; Xu, Chao; Sun, Qianwen; Wu, Shengzhou; Zhang, Kaiming; Guan, Min‐Xin; Zhou, Tian; Sun, Fei; Cai, Xiujun; Huang, Chuan; Ge, Shengfang

doi:10.1038/s41467-022-33356-z

Cited by 35 publications

(34 citation statements)

References 81 publications

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“…Since circRNAs have no free ends, they must be exported via a different mechanism. In support, our recent study has demonstrated that the evolutionarily conserved receptor Exportin-4 (XPO4) directly binds to a subset of circRNAs, but not their linear counterparts, to facilitate their nuclear export ( 15 ).…”

Section: Introductionmentioning

confidence: 90%

eIF3j inhibits translation of a subset of circular RNAs in eukaryotic cells

Song

Lin

et al. 2022

Nucleic Acids Research

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Increasing studies have revealed that a subset of circular RNAs (circRNAs) harbor an open reading frame and can act as protein-coding templates to generate functional proteins that are closely associated with multiple physiological and disease-relevant processes, and thus proper regulation of synthesis of these circRNA-derived proteins is a fundamental cellular process required for homeostasis maintenance. However, how circRNA translation initiation is coordinated by different trans-acting factors remains poorly understood. In particular, the impact of different eukaryotic translation initiation factors (eIFs) on circRNA translation and the physiological relevance of this distinct regulation have not yet been characterized. In this study, we screened all 43 Drosophila eIFs and revealed the conflicting functions of eIF3 subunits in the translational control of the translatable circRNA circSfl: eIF3 is indispensable for circSfl translation, while the eIF3-associated factor eIF3j is the most potent inhibitor. Mechanistically, the binding of eIF3j to circSfl promotes the disassociation of eIF3. The C-terminus of eIF3j and an RNA regulon within the circSfl untranslated region (UTR) are essential for the inhibitory effect of eIF3j. Moreover, we revealed the physiological relevance of eIF3j-mediated circSfl translation repression in response to heat shock. Finally, additional translatable circRNAs were identified to be similarly regulated in an eIF3j-dependent manner. Altogether, our study provides a significant insight into the field of cap-independent translational regulation and undiscovered functions of eIF3.

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Section: Introductionmentioning

confidence: 90%

eIF3j inhibits translation of a subset of circular RNAs in eukaryotic cells

Song

Lin

et al. 2022

Nucleic Acids Research

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“…Therefore, the process of circRNA nuclear export is crucial for its function. Study has shown that efficient circRNA nuclear export is a previously unappreciated layer of regulation which is critical to normal physiological function ( 77 ). The abnormalities in circRNA nuclear export lead to physiological defects ( 78 , 79 ).…”

Section: Discussionmentioning

confidence: 99%

Emerging roles of circular RNAs in cancer therapy-induced cardiotoxicity

Cheng

Qin

et al. 2023

Front. Cardiovasc. Med.

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Cancer therapy-induced cardiotoxicity (CTIC) is an important cause of death in cancer survivors which often results in the withdrawal or discontinuation of drugs. The underlying mechanisms of CTIC remain unclear. Circular RNAs (circRNAs) are a class of non-coding regulatory RNA molecules which have emerged in recent years. They are generated by back splicing and have powerful biological functions, including transcription and splicing, isolating or building macromolecular scaffolds to interfere with microRNA activity and signaling pathways, and acting as templates for translation. Moreover, circRNAs demonstrate high abundance and significant stability. CircRNAs can be used as novel biomarkers because they often function in a cell-type and tissue-specific manner. CircRNAs have attracted increasing attention in cardiovascular disease research, and recent studies exploring the role of circRNAs in CTIC have had promising results. This review will summarize the current understanding of circRNAs’ biogenesis, regulation and function. Their clinical potential as biomarkers, therapeutic agents and drug targets will also be explored.

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“…Decreases of ADAR levels in Drosophila due to high temperature will also lead to increased RNA circularisation [ 161 ]. Different to the linear mRNAs with the lack of 5′ and 3′ UTRs, the GW182-mediated circRNA degradation and the pathway controlling circRNA export from the nucleus are also conserved between Drosophila and human [ 165 , 166 , 167 , 168 ].…”

Section: Circrna In Drosophilamentioning

confidence: 99%

Noncoding RNA Regulation of Hormonal and Metabolic Systems in the Fruit Fly Drosophila

Chan

Bendena

et al. 2023

Metabolites

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The importance of RNAs is commonly recognised thanks to protein-coding RNAs, whereas non-coding RNAs (ncRNAs) were conventionally regarded as ‘junk’. In the last decade, ncRNAs’ significance and roles are becoming noticeable in various biological activities, including those in hormonal and metabolic regulation. Among the ncRNAs: microRNA (miRNA) is a small RNA transcript with ~20 nucleotides in length; long non-coding RNA (lncRNA) is an RNA transcript with >200 nucleotides; and circular RNA (circRNA) is derived from back-splicing of pre-mRNA. These ncRNAs can regulate gene expression levels at epigenetic, transcriptional, and post-transcriptional levels through various mechanisms in insects. A better understanding of these crucial regulators is essential to both basic and applied entomology. In this review, we intend to summarise and discuss the current understanding and knowledge of miRNA, lncRNA, and circRNA in the best-studied insect model, the fruit fly Drosophila.

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Exportin 4 depletion leads to nuclear accumulation of a subset of circular RNAs

Cited by 35 publications

References 81 publications

eIF3j inhibits translation of a subset of circular RNAs in eukaryotic cells

eIF3j inhibits translation of a subset of circular RNAs in eukaryotic cells

Emerging roles of circular RNAs in cancer therapy-induced cardiotoxicity

Noncoding RNA Regulation of Hormonal and Metabolic Systems in the Fruit Fly Drosophila

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