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Nuclear export of circular RNA

ABSTRACT: Circular RNAs (circRNAs), which can function as regulators of gene expression, are formed by back-splicing of precursor mRNAs in the nucleus. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here, we uncover a pathway specific for 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 nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Analysis of nuclear circRNA binding proteins reveals that interaction of IGF2BP1 with circRNA is enhanced by Ran-GTP, whereas its interaction with linear RNA is inhibited by Ran-GTP. Depletion or knockout of Exportin-2 specifically inhibits nuclear export of circRNA, while formation of an Exportin-2 circRNA export complex requires Ran-GTP and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Exportin-2 to export circRNAs in a mechanism analogous to protein export, rather than mRNA export.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235899 | GEO | 2023/12/09

REPOSITORIES: GEO

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