In-silico studies to analyse the possible interactions of CircPPP1R12A translated peptide with Mst proteins.

The Mammalian sterile 20 kinase (Mst) pathway controls organ development by regulating cell proliferation through apoptosis and has a noncanonical role in cancer. Overexpression of the peptide translated from circular RNA, circPPP1R12A, corelated with the activation of YAP, an oncogene whose expression is triggered upon dysregulation of Mst signalling. The exact mode of molecular interaction(s) leading to inactivation of the Mst pathway by this peptide is hitherto unknown. Mst1 and Mst2 are two prime proteins that require dimerization with their scaffold protein, Sav1 at the early step of Mst signalling. We have investigated the interaction of Mst1/2 proteins with this peptide using molecular docking and molecular dynamics simulation studies. The amino acids involved in binding of the peptide were identified and a comparison between the binding interfaces of Mst1/2 - peptide with Mst1/2 - Sav1 complexes indicated that the binding of the peptide to these Mst proteins may prevent the interactions of these proteins with Sav1. Studying the possible binding modes of Sav1 to the Mst proteins already complexed with the peptide further confirmed that the binding of the peptide may hinder their activation. The in-silico study indicated for the first time the possible molecular mechanism of how the peptide can promote cancer by interfering with the Mst pathway.

Characterizations of a novel peptide encoded by a circular RNA using in-silico analyses.

CircRNAs have gained importance in recent times due to their involvement in gene regulation and also in the prognosis of cancer. Generally, the circRNA directly interact with miRNA or RNA binding proteins to exert their action, but some of them can be translated. These translated peptides often participate in the regulation of cellular processes. The circPPP1R12A translated peptide has been shown to influence the functioning of the Mst pathway. The Mst signaling is noteworthy for its role in the process of development, but it also has a function as a regulator of apoptosis, which is significant for regulation of cancer. Overexpression of this novel peptide deactivates the Mst signaling to induce the expression of the proliferative oncogene, Yap. Its molecular interaction with the molecules in the Mst pathway is hitherto unknown. In this short report we present our findings from in-silico studies the plausible structure of the peptide through bioinformatics and dynamics simulation studies. This is the first such report on the structure of the novel peptide encoded by circPPP1R12A, which could be important to predict in future its molecular interactions to understand its functionality.