A systematic analysis of circRNAs in subnuclear compartments
CircRNAs are an important class of RNAs with diverse cellular functions in human physiology and disease. A thorough knowledge of circRNAs including their biogenesis and subcellular distribution is important to understand their roles in a wide variety of processes. However, the analysis of circRNAs f...
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| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | RNA Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2024.2395718 |
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| author | Andre Brezski Justin Murtagh Marcel H. Schulz Kathi Zarnack |
| author_facet | Andre Brezski Justin Murtagh Marcel H. Schulz Kathi Zarnack |
| author_sort | Andre Brezski |
| collection | DOAJ |
| description | CircRNAs are an important class of RNAs with diverse cellular functions in human physiology and disease. A thorough knowledge of circRNAs including their biogenesis and subcellular distribution is important to understand their roles in a wide variety of processes. However, the analysis of circRNAs from total RNA sequencing data remains challenging. Therefore, we developed Calcifer, a versatile workflow for circRNA annotation. Using Calcifer, we analysed APEX-Seq data to compare circRNA occurrence between whole cells, nucleus and subnuclear compartments. We generally find that circRNAs show higher abundance in whole cells compared to nuclear samples, consistent with their accumulation in the cytoplasm. The notable exception is the single-exon circRNA circCANX(9), which is unexpectedly enriched in the nucleus. In addition, we observe that circFIRRE prevails over the linear lncRNA FIRRE in both the cytoplasm and the nucleus. Zooming in on the subnuclear compartments, we show that circRNAs are strongly depleted from nuclear speckles, indicating that excess splicing factors in this compartment counteract back-splicing. Our results thereby provide valuable insights into the subnuclear distribution of circRNAs. Regarding circRNA function, we surprisingly find that the majority of all detected circRNAs possess complete open reading frames with potential for cap-independent translation. Overall, we show that Calcifer is an easy-to-use, versatile and sustainable workflow for the annotation of circRNAs which expands the repertoire of circRNA tools and allows to gain new insights into circRNA distribution and function. |
| format | Article |
| id | doaj-art-9998bf91e67f4d61935476da96e7a7e2 |
| institution | Kabale University |
| issn | 1547-6286 1555-8584 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | RNA Biology |
| spelling | doaj-art-9998bf91e67f4d61935476da96e7a7e22024-12-11T07:47:44ZengTaylor & Francis GroupRNA Biology1547-62861555-85842024-12-0121190191610.1080/15476286.2024.2395718A systematic analysis of circRNAs in subnuclear compartmentsAndre Brezski0Justin Murtagh1Marcel H. Schulz2Kathi Zarnack3Buchmann Institute for Molecular Life Sciences (BMLS) & Institute of Molecular Biosciences, Goethe University Frankfurt, Frankfurt am Main, Hesse, GermanyDepartment of Medicine, Institute for Computational Genomic Medicine and Institute of Cardiovascular Regeneration, Goethe University Frankfurt, Frankfurt am Main, Hesse, GermanyDepartment of Medicine, Institute for Computational Genomic Medicine and Institute of Cardiovascular Regeneration, Goethe University Frankfurt, Frankfurt am Main, Hesse, GermanyBuchmann Institute for Molecular Life Sciences (BMLS) & Institute of Molecular Biosciences, Goethe University Frankfurt, Frankfurt am Main, Hesse, GermanyCircRNAs are an important class of RNAs with diverse cellular functions in human physiology and disease. A thorough knowledge of circRNAs including their biogenesis and subcellular distribution is important to understand their roles in a wide variety of processes. However, the analysis of circRNAs from total RNA sequencing data remains challenging. Therefore, we developed Calcifer, a versatile workflow for circRNA annotation. Using Calcifer, we analysed APEX-Seq data to compare circRNA occurrence between whole cells, nucleus and subnuclear compartments. We generally find that circRNAs show higher abundance in whole cells compared to nuclear samples, consistent with their accumulation in the cytoplasm. The notable exception is the single-exon circRNA circCANX(9), which is unexpectedly enriched in the nucleus. In addition, we observe that circFIRRE prevails over the linear lncRNA FIRRE in both the cytoplasm and the nucleus. Zooming in on the subnuclear compartments, we show that circRNAs are strongly depleted from nuclear speckles, indicating that excess splicing factors in this compartment counteract back-splicing. Our results thereby provide valuable insights into the subnuclear distribution of circRNAs. Regarding circRNA function, we surprisingly find that the majority of all detected circRNAs possess complete open reading frames with potential for cap-independent translation. Overall, we show that Calcifer is an easy-to-use, versatile and sustainable workflow for the annotation of circRNAs which expands the repertoire of circRNA tools and allows to gain new insights into circRNA distribution and function.https://www.tandfonline.com/doi/10.1080/15476286.2024.2395718CircRNAsubnuclear compartmentsworkflownuclear specklescircRNA translation |
| spellingShingle | Andre Brezski Justin Murtagh Marcel H. Schulz Kathi Zarnack A systematic analysis of circRNAs in subnuclear compartments RNA Biology CircRNA subnuclear compartments workflow nuclear speckles circRNA translation |
| title | A systematic analysis of circRNAs in subnuclear compartments |
| title_full | A systematic analysis of circRNAs in subnuclear compartments |
| title_fullStr | A systematic analysis of circRNAs in subnuclear compartments |
| title_full_unstemmed | A systematic analysis of circRNAs in subnuclear compartments |
| title_short | A systematic analysis of circRNAs in subnuclear compartments |
| title_sort | systematic analysis of circrnas in subnuclear compartments |
| topic | CircRNA subnuclear compartments workflow nuclear speckles circRNA translation |
| url | https://www.tandfonline.com/doi/10.1080/15476286.2024.2395718 |
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