A novel melanoma therapeutic target: Elucidating the structure and mapping functional domains of the lncRNA SAMMSON The incidence of melanoma has doubled since the 1970?s, thus, there is an urgent need for a cure for this cancer. SAMMSON (survival associated mitochondrial melanoma-specific oncogenic noncoding) is a long- noncoding RNA (lncRNA) expressed exclusively in malignant melanoma cells. In melanoma cells, depletion of SAMMSON induces apoptosis. This phenomenon suggests that SAMMSON is essential for melanoma cell survival, making SAMMSON an attractive target for anti-cancer therapy. SAMMSON interacts with p32, a protein necessary for mitochondrial maintenance; little else known about SAMMSON structure and function. To pursue a potential therapy targeting SAMMSON, it is necessary to determine the secondary structural ensembles that SAMMSON adopts in vivo and the SAMMSON structural requirements for interaction with p32. Although lncRNAs are implicated in a multitude of cellular processes, only a few lncRNA structures are known. Among those structures, specific domains have been found to be essential for lncRNA function. Thus, we propose to perform the following studies: (1) We will model the in vitro and in vivo secondary structures of SAMMSON using SHAPE-MaP, a high throughput RNA chemical probing technology, and (2) We will identify the domains within SAMMSON necessary for SAMMSON:p32 interaction. Completion of these Aims will provide crucial information necessary to design inhibitors of SAMMSON:p32 interaction that may be effective anti-melanoma agents.
The lncRNA SAMMSON is specifically expressed in malignant melanoma cells, and upon depletion of SAMMSON, melanoma cells undergo apoptosis. SAMMSON localizes the protein p32 to the mitochondria, and this protein is necessary for mitochondrial function. We aim to model the secondary structure of SAMMSON and identify the structural domains required for SAMMSON to interact with p32.
