Nuclear export of circular RNA.

Autor: Ngo LH; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia., Bert AG; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia., Dredge BK; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia.; Adelaide Centre for Epigenetics, School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.; South Australian immunoGENomics Cancer Institute (SAiGENCI), Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia., Williams T; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland., Murphy V; Genome Stability Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia., Li W; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.; Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine and Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen, China., Hamilton WB; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia., Carey KT; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia., Toubia J; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia., Pillman KA; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia.; Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia., Liu D; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia., Desogus J; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.; University of Basel, Basel, Switzerland., Chao JA; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland., Deans AJ; Genome Stability Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia., Goodall GJ; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia. greg.goodall@unisa.edu.au.; Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia. greg.goodall@unisa.edu.au.; Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia. greg.goodall@unisa.edu.au., Wickramasinghe VO; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. vi.wickramasinghe@petermac.org.; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia. vi.wickramasinghe@petermac.org.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Mar; Vol. 627 (8002), pp. 212-220. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1038/s41586-024-07060-5
Abstrakt: Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells 1-5 , are formed by back-splicing of precursor mRNAs in the nucleus 6-10 . circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here we identify a pathway that is specific for the nuclear export of circular RNA. This pathway requires Ran-GTP, exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter CRM1 selectively increases the nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA-binding proteins reveals that interaction between IGF2BP1 and circRNA is enhanced by Ran-GTP. The formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with exportin-2, circRNA and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and exportin-2 to export circRNAs in a mechanism that is analogous to protein export, rather than mRNA export.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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