The long noncoding RNA (lncRNA) Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is oncogenic, accumulates in many cancerous tissues, and enhances cancer proliferation and invasion. The 3’-end of this RNA forms a triple helix that protects the entire lncRNA from 3’-5’ exonuclease activity. This triple helix is a 94 nucleotide long RNA that consists of different structural regions including P1 and P2 stems, a triplex region, and a linker region at the bottom of P1 stem. Previous studies have conducted mutational analysis on the various regions of MALAT1 triple helix (M1TH) to determine their role on its function. Here, we characterize the effect of the basal linker region on M1TH’s stability using thermostability and biochemical protection assays of different linker mutants. Our results show that all the linker mutants are less stable than M1TH indicating the significance of this region to M1TH’s stability and function. We use SAXS to investigate the potential structure formation in M1TH linker region and determine a helical structure formation in this region that stabilizes the 3’ end despite being 40-50 Å away. Our work identifies a structural element that could serve as a site for targeting this ncRNA and demonstrates the capability of long-range structural elements within RNA to influence its function.

Investigating the role of the MALAT1 ENE basal linker in stabilizing triplex formation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.