Nuclear export of circular RNA

Ngo，Linh H.1; Bert，Andrew G.2; Dredge，B. Kate2,10,11; Williams，Tobias1,6; Murphy，Vincent3; Li，Wanqiu1,4; Hamilton，William B.1; Carey，Kirstyn T.1; Toubia，John2; Pillman，Katherine A.2,5; Liu，Dawei2; Desogus，Jessica6,7; Chao，Jeffrey A.6; Deans，Andrew J.3; Goodall，Gregory J.2,5,8; Wickramasinghe，Vihandha O.1,9

2024-03-07

10.1038/s41586-024-07060-5

Nature   影响因子和分区

0028-0836

1476-4687

Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells, 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 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.

SCI

英语

其他

BIOLOGY & BIOCHEMISTRY ; CLINICAL MEDICINE ; MULTIDISCIPLINARY ; PLANT & ANIMAL SCIENCE ; ENVIRONMENT/ECOLOGY ; SOCIAL SCIENCES, GENERAL ; MICROBIOLOGY ; ECONOMICS BUSINESS ; IMMUNOLOGY ; MATERIALS SCIENCE ; COMPUTER SCIENCE ; SPACE SCIENCE ; MOLECULAR BIOLOGY & GENETICS ; CHEMISTRY ; NEUROSCIENCE & BEHAVIOR ; PHYSICS ; GEOSCIENCES ; ENGINEERING

2-s2.0-85185134199

Scopus

1.RNA Biology and Cancer Laboratory,Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology,University of Melbourne,Melbourne,Australia
2.Centre for Cancer Biology,University of South Australia and SA Pathology,Adelaide,Australia
3.Genome Stability Unit,St Vincent’s Institute of Medical Research,Fitzroy,Australia
4.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
5.Department of Molecular and Biomedical Science,University of Adelaide,Adelaide,Australia
6.Friedrich Miescher Institute for Biomedical Research,Basel,Switzerland
7.University of Basel,Basel,Switzerland
8.Department of Medicine,University of Adelaide,Adelaide,Australia
9.Department of Biochemistry and Pharmacology,Bio21 Molecular Science and Biotechnology Institute,The University of Melbourne,Parkville,Australia
10.Adelaide Centre for Epigenetics,School of Biomedicine,Faculty of Health and Medical Sciences,University of Adelaide,Adelaide,Australia
11.South Australian immunoGENomics Cancer Institute (SAiGENCI),Faculty of Health and Medical Sciences,University of Adelaide,Adelaide,Australia

Ngo，Linh H.,Bert，Andrew G.,Dredge，B. Kate,et al. Nuclear export of circular RNA[J]. Nature,2024,627(8002):212-220.

Ngo，Linh H..,Bert，Andrew G..,Dredge，B. Kate.,Williams，Tobias.,Murphy，Vincent.,...&Wickramasinghe，Vihandha O..(2024).Nuclear export of circular RNA.Nature,627(8002),212-220.

Ngo，Linh H.,et al."Nuclear export of circular RNA".Nature 627.8002(2024):212-220.