Journal article
Nuclear export of circular RNA
LH Ngo, AG Bert, BK Dredge, T Williams, V Murphy, W Li, WB Hamilton, KT Carey, J Toubia, KA Pillman, D Liu, J Desogus, JA Chao, AJ Deans, GJ Goodall, VO Wickramasinghe
Nature | Published : 2024
Abstract
Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1–5, are formed by back-splicing of precursor mRNAs in the nucleus6–10. 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 k..
View full abstractGrants
Awarded by Victorian Cancer Agency
Funding Acknowledgements
We thank R. Laskey for reading the manuscript; K. Cowley and the staff at the Victorian Centre for Functional Genomics for help with image analysis and the generation of a stable Cas9-expressing CAL51 cell line; the staff at the CCB ACRF Cancer Genomics Facility for assistance with RNA-seq; N. Williamson and the staff at the Bio21 protein characterization facilities for assistance with proteomics and mass photometry; and D. Jans for providing the KPNA2 protein. We acknowledge funding from the NHMRC (1127745 and 2003545 to V.O.W., and 1089167, 1126711 and research fellowship 1118170 to G.J.G.) and the National Breast Cancer Foundation (IN-16-072-2036220). K.A.P. was supported by a Royal Adelaide Hospital Research Committee Florey Fellowship. V.O.W. has been supported by an Innovation fellowship from veski and a mid-career fellowship from the Victorian Cancer Agency. V.O.W. thanks R. Wickramasinghe posthumously.