Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response.

Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity / Rossi, Francesca; BELTRAN NEBOT, Manuel; Damizia, Michela; Grelloni, Chiara; Colantoni, Alessio; Setti, Adriano; DI TIMOTEO, Gaia; Dattilo, Dario; Alvaro, Centrón-Broco; Nicoletti, Carmine; Fanciulli, Maurizio; Lavia, Patrizia; Bozzoni, Irene. - In: MOLECULAR CELL. - ISSN 1097-4164. - 82:1(2021), pp. 75-89. [10.1016/j.molcel.2021.11.032]

Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity

Francesca Rossi
Co-primo
;
Manuel Beltran
Co-primo
;
Michela Damizia;Chiara Grelloni;Alessio Colantoni;Adriano Setti;Gaia Di Timoteo;Dario Dattilo;Alvaro Centrón-Broco;Carmine Nicoletti;Irene Bozzoni
Ultimo
2021

Abstract

Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response.
2021
RNA-RNA interactioncirc; RNAsmicrotubules; CKAP5; anti-cancer treatments; rhabdomyosarcoma
01 Pubblicazione su rivista::01a Articolo in rivista
Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity / Rossi, Francesca; BELTRAN NEBOT, Manuel; Damizia, Michela; Grelloni, Chiara; Colantoni, Alessio; Setti, Adriano; DI TIMOTEO, Gaia; Dattilo, Dario; Alvaro, Centrón-Broco; Nicoletti, Carmine; Fanciulli, Maurizio; Lavia, Patrizia; Bozzoni, Irene. - In: MOLECULAR CELL. - ISSN 1097-4164. - 82:1(2021), pp. 75-89. [10.1016/j.molcel.2021.11.032]
File allegati a questo prodotto
File Dimensione Formato  
Rossi_Circular_2022.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 4.83 MB
Formato Adobe PDF
4.83 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1600938
Citazioni
  • ???jsp.display-item.citation.pmc??? 28
  • Scopus 36
  • ???jsp.display-item.citation.isi??? 30
social impact