Emerging role of G-quadruplexes in alternative splicing regulation

Alternative splicing (AS) allows the production of several distinct proteins from a single protein-coding gene, thereby increasing the complexity of the proteome. In this review, we focus on the role of G-quadruplexes (G4s) in AS. G4s are noncanonical secondary structures that may form in guanine-rich loci of nucleic acids. G4s may assemble in both G-rich DNA (dG4s) and RNA (rG4s) and influence various processes, such as DNA replication, transcription, AS, or translation. We present the increasingly emerging roles of rG4s in AS regulation and discuss the potential mechanisms behind these roles. Finally, we highlight human disorders associated with dysfunctions in these processes and consider the possible use of rG4s as intervention points for these conditions, with a particular focus on cancer.