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Supplementary Figures 1-9 from Exon Junction Complex Mediates the Cap-Independent Translation of Circular RNA

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posted on 2023-11-01, 08:02 authored by Hui-Hsuan Lin, Chiu-Yuan Chang, Yi-Ren Huang, Che-Hung Shen, Yu-Chen Wu, Kai-Li Chang, Yueh-Chun Lee, Ya-Chi Lin, Wen-Chien Ting, Han-Ju Chien, Yi-Feng Zheng, Chien-Chen Lai, Kuei-Yang Hsiao

Figure S1. CircRNA candidates identified from 5 polyribosome profiling studies. Figure S2. Analysis of common targets for circSDHAF2. Figure S3. circSDHAF2 associated with actively translating ribosomes. Figure S4. CircSDHAF2 produces proteins. Figure S5. Intron 2 does not promote nuclear export. Figure S6. Spliceosome inhibitor suppressed circCoding reporter activity. Figure S7. Elevated splicing-mediated cap-independent translation activity in CRC cells. Figure S8. Knockdown of circSDHAF2 suppresses development of tumorspheres. Figure S9. Demographic information of CRC patients.

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National Science and Technology Council (NSTC)

Animal Biotechnology Center, National Chung Hsing University (Animal Biotechnology Center)

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ARTICLE ABSTRACT

Evidence that circular RNAs (circRNA) serve as protein template is accumulating. However, how the cap-independent translation is controlled remains largely uncharacterized. Here, we show that the presence of intron and thus splicing promote cap-independent translation. By acquiring the exon junction complex (EJC) after splicing, the interaction between circRNA and ribosomes was promoted, thereby facilitating translation. Prevention of splicing by treatment with spliceosome inhibitor or mutating splicing signal hindered cap-independent translation of circRNA. Moreover, EJC-tethering using Cas13 technology reconstituted EJC-dependent circRNA translation. Finally, the level of a coding circRNA from succinate dehydrogenase assembly factor 2 (circSDHAF2) was found to be elevated in the tumorous tissues from patients with colorectal cancer, and shown to be critical in tumorigenesis of colorectal cancer in both cell and murine models. These findings reveal that EJC-dependent control of circSDHAF2 translation is involved in the regulation of oncogenic pathways. EJC-mediated cap-independent translation of circRNA is implicated in the tumorigenesis of colorectal cancer.

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    Molecular Cancer Research

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    Keywords

    Gastrointestinal CancersGene RegulationPosttranscriptional and translational controlGenome BiologyNon-coding RNAs & microRNAsProgression, Invasion & MetastasisTumor progression

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