Two recent studies by the Department of Biology and Biotechnology “Charles Darwin” of Sapienza University of Rome and the Italian Institute of Technology (IIT), conducted by the research team led by Irene Bozzoni, demonstrated new regulatory functions for circular RNAs.

These molecules, which are involved in several mechanisms that regulate gene expression, are particularly abundant in the human brain, and their alteration has been implicated in several complex neurological disorders such as Parkinson's, Alzheimer's and autism spectrum disorders. Circular RNAs have also been shown to play a key role in tumours, where they are often altered.

The research ‘A tripartite circRNA/mRNA/miRNA interaction regulates glutamatergic signalling in the mouse brain’, published in the journal Cell Reports and to which Mariangela Morlando also contributed for Sapienza, identified a never-before-described mechanism for circular RNAs, based on the interactions that a circular RNA has with both microRNAs and messenger RNAs associated with excitatory (glutamatergic) signalling pathways.

In particular, the researchers found that circular RNA regulates the localisation of microRNA at synapses, where the latter controls the translation of messenger RNAs encoding excitatory receptors: the specific role as a 'transporter' molecule differs from the functions previously attributed to circular RNA and gives the molecule fascinating new levels of regulation.

The study ‘BRCA1 levels and DNA damage response are controlled by the competitive binding of circHIPK3 or FMRP to the BRCA1 mRNA’, published in the journal Molecular Cell and funded by the Fondazione AIRC per la Ricerca sul Cancro, focuses on a novel mechanism of tumour-associated regulation of gene expression mediated by a circular RNA.

In particular, they proved that a specific circular RNA, circHIPK3, regulates the production of the BRCA1 protein, whose control is essential in several tumour types, including rhabdomyosarcoma, one of the most common and aggressive childhood cancers, glioblastoma, ovarian and breast cancer.

References:

A tripartite circRNA/mRNA/miRNA interaction regulates glutamatergic signaling in the mouse brain – Silenzi V., D’Ambra E., Santini T., D’Uva S., Setti A., Salvi N., Nicoletti C., Cordella F., Mongiardi B., Cavezza D., Liessi N., Ferrucci L., Ragozzino D., Armirotti A., Di Angelantonio S., De Leonibus E., Bozzoni I. and Morlando M. – Cell Rep 2024 doi:10.1016/j.celrep.2024.114766

BRCA1 levels and DNA damage response are controlled by the competitive binding of circHIPK3 or FMRP to the BRCA1 mRNA- Chiara Grelloni, Raffaele Garraffo, Adriano Setti, Francesca Rossi, Giovanna Peruzzi, Mario Cinquanta, Maria Carmela Di Rosa, Marco Alessandro Pierotti, Manuel Beltran & Irene Bozzoni – Mol Cell  DOI: 10.17632/fk8bm3rxh2.1

Further information

Irene Bozzoni    

Dipartimento di Biologia e biotecnologie Charles Darwin, Sapienza Università di Roma           irene.bozzoni@uniroma1.it                                                                                                        

Mariangela Morlando 

Dipartimento di Biologia e biotecnologie Charles Darwin, Sapienza Università di Roma    mariangela.morlando@uniroma1.it