Short tandem repeats (STRs) are small, repeated sequences of DNA scattered throughout the human genome. While some of these repeats are known to cause severe genetic disorders, scientists are now beginning to understand how more subtle changes in these sequences might influence how genes are turned on or off.

Researchers from Sweet Briar College explored how transcribed STRs might affect RNA structure. RNA is the molecule that carries genetic instructions from DNA to make proteins, and its shape can influence how well it functions. Using computational tools and data from the 1000 Genomes Project, the team identified more than 17,000 STRs that appear to change the way RNA folds.

Short tandem repeat (STR) variants affect RNA secondary structure and are possibly associated with gene expression

(left) The effect of STR variants on RNA folding (fSTRs) was inferred by comparing secondary structures with bpRNA-align and affinity propagation clustering. Five variants of a penta-repeat (TGGGG) in an SH2B3 intron fall into two clusters (A and B). (right) Gene expression (rpkm) values for a collection of samples are grouped by genotype after mapping each variant to its cluster assignment. Since each sample has two alleles there are three combinations of cluster assignments (independent axis). We perform a test of the null: no difference in gene expression between groups. The null is rejected (p < .01) suggesting an association between RNA folding and SH2B3 expression.

Some of these STRs may alter features like loops in the RNA molecule, which could impact how it is spliced, transported, or translated into proteins. Interestingly, the researchers found that the effect on RNA accessibility depends on the type of repeat, revealing a level of complexity that surprised even the researchers. Their findings suggest a new way that genetic variation might influence gene expression and point to exciting possibilities for future research.