Systematic loss-of-function screens identify pathway-specific functional circular RNAs.
Nat Cell Biol
; 26(8): 1359-1372, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-39095657
ABSTRACT
Circular RNA (circRNA) is covalently closed, single-stranded RNA produced by back-splicing. A few circRNAs have been implicated as functional; however, we lack understanding of pathways that are regulated by circRNAs. Here we generated a pooled short-hairpin RNA library targeting the back-splice junction of 3,354 human circRNAs that are expressed at different levels (ranging from low to high) in humans. We used this library for loss-of-function proliferation screens in a panel of 18 cancer cell lines from four tissue types harbouring mutations leading to constitutive activity of defined pathways. Both context-specific and non-specific circRNAs were identified. Some circRNAs were found to directly regulate their precursor, whereas some have a function unrelated to their precursor. We validated these observations with a secondary screen and uncovered a role for circRERE(4-10) and circHUWE1(22,23), two cell-essential circRNAs, circSMAD2(2-6), a WNT pathway regulator, and circMTO1(2,RI,3), a regulator of MAPK signalling. Our work sheds light on pathways regulated by circRNAs and provides a catalogue of circRNAs with a measurable function.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proliferación Celular
/
ARN Circular
Límite:
Humans
Idioma:
En
Revista:
Nat Cell Biol
/
Nat. cell biol
/
Nature cell biology
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia