RiboSnitches are single nucleotide variants that change the secondary structures of RNA. These structural changes can have a regulatory or functional impact on the RNA. Many inherited single nucleotide variants function as riboSNitches. We wanted to investigate the potential of somatic mutations to act as riboSNitches. We determined the secondary structure of two cancer-associated mRNAs, TPT1 and LCP1, using the chemical probing SHAPE-Map technique. Both of these mRNAs are highly structured and have similar folds in vivo and in vitro. We analyzed the structural impact of all the synonymous somatic mutations identified in the COSMIC cancer sequencing database for both TPT1 and LCP1 mRNAs. In TPT1 we also tested several inherited variants. We found that both somatic and inherited variants can be riboSNitches, at approximately the same ratio. Our results are in accord with previous work indicating that ~15% of SNVs are capable of acting as riboSNitches. Although the impact of non-coding and synonymous somatic mutations are difficult to measure, it is becoming clear that these mutations can contribute to cancer progression and phenotype. The majority of our identified riboSNitches are detrimental according to FATHMM-MKL functional impact prediction. Our experiments indicate that a substantial fraction of somatic mutations can cause a measurable change to RNA structure, potentially changing the regulatory or functional behavior of that mRNA.

Citation Format: Lela L. Lackey, Aaztli Coria, Chanin Tolson, Evonne McArthur, Alain Laederach. Somatic and inherited riboSnitches in TPT1 and LCP1 mRNA secondary structures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 505. doi:10.1158/1538-7445.AM2017-505