Long non-coding RNAs (lncRNAs) have emerged as key players in gene regulation. However, our incomplete understanding of the structure of lncRNAs has hindered molecular characterization of their function. Maternally expressed gene 3 (Meg3) lncRNA is a tumor suppressor that is downregulated in various types of cancer. Mechanistic studies have reported a role for Meg3 in epigenetic regulation by interacting with chromatin-modifying complexes such as the polycomb repressive complex 2 (PRC2), guiding them to genomic sites via DNA-RNA triplex formation. Resolving the structure of Meg3 RNA and characterizing its interactions with cellular binding partners will deepen our understanding of tumorigenesis and provide a framework for RNA-based anti-cancer therapies. Herein, we characterize the architectural landscape of Meg3 RNA and its interactions with PRC2 from a functional standpoint.