Structure-function activity study of the unusual protein MAPK1-109aa encoded by the non-coding circular RNA...

Circular RNAs are closed-loop single-stranded non-coding RNA molecules. Once considered as transcriptional junks, their physiological roles in the process of tumourigenesis have recently been being identified. In spite of belonging to the class of non-coding RNAs, some of them have distinct protein coding abilities. The circular RNA hsa_circ_0004872, which encodes the protein MAPK1-109aa, is one such example. This protein is associated with gastric cancer pathway, as, MAPK1-109aa can bind to MEK1 and inhibit the phosphorylation of MAPK1 and this further disturbs the downstream signalling and activation processes necessary for the onset of gastric cancer. However, the residue level details of the binding interactions of MAPK1-109aa and its partners are not yet available. Therefore, our aim is to delineate the structural details and folding pattern of the protein and provide insight on its mode of interactions with its binding partner, MEK1. Furthermore, we tried to determine whether MAPK1-109aa has its role in any pathway(s) other than gastric cancer. Through the technique of network analyses, we could predict that the protein is associated with the pathways that lead to conditions like neurodegenerations and others. This work is the first of its kind, which elucidates the residue-level pattern of interactions of MAPK1-109aa with MEK1 in gastric cancer onset as well as the association of MAPK1-109aa with other diseases. This work highlights the potential application of MAPK1-109aa as a therapeutic agent for the treatment of gastric cancer.