Figure 4

CTG repeat-binding miRNAs and their repression of pairs of extensively overlapping sites. (a) A diagram showing how a region of NM_173354 containing seven CTG repeats can result in six binding site seeds (CTGCTG) and five pairs of extensively overlapping sites (pairs of binding sites 3 bp apart). (b) Seven miRNAs containing CAG-rich seed regions that are predicted to bind to CTG repeats. Only hsa-miR-214 has mismatches in the seed region. (c) Number of overlapping binding sites versus relative expression for seven CTG repeat-binding miRNAs. In general, as the number of pairs of extensively overlapping sites increases, the degree of repression increases. In particular, mirs-107, -103, and -15a show a strong correlation. (d) Decreased relative expression of wild-type DMPK with respect to seven CTG repeat-binding miRNAs suggests repression of mutated DMPK by miRNAs could play a role in DM1. Targets with no overlapping pairs of sites served as control and showed no overall repression.