Nuclear export of circular RNA
- Author(s)
- Ngo, LH; Bert, AG; Dredge, BK; Williams, T; Murphy, V; Li, W; Hamilton, WB; Carey, KT; Toubia, J; Pillman, KA; Liu, D; Desogus, J; Chao, JA; Deans, AJ; Goodall, GJ; Wickramasinghe, VO;
- Journal Title
- Nature
- Publication Type
- Research article
- Abstract
- 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.
- Publisher
- Springer Nature
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1038/s41586-024-07060-5
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-03-13 05:11:31
Last Modified: 2024-03-13 05:25:38