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Wiley Interdiscip Rev RNA. 2015 Sep-Oct;6(5):517-32. doi: 10.1002/wrna.1291. Epub 2015 Jun 26.

The potential of the riboSNitch in personalized medicine.

Author information

1
Department of Biology, University of North Carolina, Chapel Hill, NC, USA.
2
Institute for Genomic Medicine, Columbia University, New York, NY, USA.
3
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
4
Bioinformatics and Computational Biology Program, University of North Carolina, Chapel Hill, NC, USA.

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.

PMID:
26115028
PMCID:
PMC4543445
DOI:
10.1002/wrna.1291
[Indexed for MEDLINE]
Free PMC Article

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