Dario Dattilo

Sapienza University, Rome, Italy

Thursday 8 June 2023, 17.00

Deciphering the role of N6-Methyladenosine in the metabolism of circular RNAs in rhabdomyosarcoma



Among RNA modifications, N6-Methyladenosine (m6A) is well known for its contribution to different processes controlling linear RNA metabolism, including splicing, stability, and translation of mRNAs. Conversely, the effects of m6A on circular RNAs (circRNAs) are still poorly understood. CircRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction, whereby a downstream 5′ splice donor site is joined to an upstream 3′ splice acceptor site. Although circRNAs are considered to be non-coding, recent studies have indicated that some of these molecules are also translated into proteins. Starting from circZNF609 as a study-case, I will discuss the ability of m6A to modulate both the biogenesis and the translation of circRNAs. I will also show how this mechanism can justify the alteration of circRNA expression observed in the pathological condition of rhabdomyosarcoma (RMS), the most diffused soft tissue sarcoma in children and adolescents. Circularization is enhanced in RMS when compared to human wild-type myoblasts. Moreover, the deregulation of a subset of circRNAs is ascribable to the altered expression of m6A modulators, which contribute to RMS progression. Finally, I will introduce the RNA helicase DDX5 as a novel mediator of the backsplicing reaction and a co-factor of the m6A regulatory machinery in RMS.


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