title: The potential of the riboSNitch in personalized medicine.
abstract: RNA conformation plays a significant role in stability, ligand binding, transcription, and translation. Single nucleotide variants (SNVs) have the potential to disrupt specific structural elements because RNA folds in a sequence-specific manner. A riboSNitch is an element of RNA structure with a specific function that is disrupted by an SNV or a single nucleotide polymorphism (SNP; or polymorphism; SNVs occur with low frequency in the population, <1%). The riboSNitch is analogous to a riboswitch, where binding of a small molecule rather than mutation alters the structure of the RNA to control gene regulation. RiboSNitches are particularly relevant to interpreting the results of genome-wide association studies (GWAS). Often GWAS identify SNPs associated with a phenotype mapping to noncoding regions of the genome. Because a majority of the human genome is transcribed, significant subsets of GWAS SNPs are putative riboSNitches. The extent to which the transcriptome is tolerant of SNP-induced structure change is still poorly understood. Recent advances in ultra high-throughput structure probing begin to reveal the structural complexities of mutation-induced structure change. This review summarizes our current understanding of SNV and SNP-induced structure change in the human transcriptome and discusses the importance of riboSNitch discovery in interpreting GWAS results and massive sequencing projects.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Solem
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC, USA.|Institute for Genomic Medicine, Columbia University, New York, NY, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Halvorsen
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Silvia B V
authors.initials: SB
authors.lastname: Ramos
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC, USA.|Bioinformatics and Computational Biology Program, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Alain
authors.initials: A
authors.lastname: Laederach
mesh_terms: D000818:Animals; D055106:Genome-Wide Association Study; D006801:Humans; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine / Q000379:methods*; D012313:RNA / Q000235:genetics*; D059370:RNA Folding; D058928:Riboswitch
chemical_list: D058928:Riboswitch; D012313:RNA