Ap4A-capped RNA: A new layer of gene expression regulation

The recent discovery of non-canonical RNA caps, such as NAD and CoA, has fundamentally changed our understanding of the structural and functional diversity of RNA in all types of cells. In our laboratory, we have recently identified a new type of RNA cap in mammalian cells—diadenosine tetraphosphate (Ap4A). Ap4A has been known for several decades as an intracellular signaling molecule; however, its function in the context of RNA has not yet been described.

Our preliminary results indicate that RNA carrying an Ap4A cap is not translated under standard conditions. At the same time, using a newly developed sequencing method, we demonstrated the presence of Ap4A on mRNA, i.e., protein-coding RNA. These findings suggest that Ap4A-capped mRNA may represent a new regulatory layer of gene expression, or alternatively that Ap4A serves as a transient structure that is subsequently removed and replaced by the canonical cap.

Using proteomic analysis, we further identified a set of proteins that specifically interact with Ap4A-RNA, indicating the existence of a previously unknown regulatory mechanism. The aim of this doctoral thesis is to elucidate the biological role of Ap4A-RNA through a detailed study of interactions between Ap4A-RNA and its binding proteins, both in vitro and in cellulo.

Study program: Developmental and Cell Biology