The length of uninterrupted CAG repeats in stem regions of repeat disease associated hairpins determines the amount of short CAG oligonucleotides that are toxic to cells through RNA interference.

In contrast, the increase in enrichment with longer TNR length was much less pronounced in genes containing CAG TNRs and all but one did not reach statistical significance even though the number of genes containing either CAG or CUG TNRs for each TNR length was comparable (numbers in bottom panels in Fig. 1D ).

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These data are highly significant in the light of our recent discovery that CAG-based siRNAs, when entering the RISC, become super toxic to cancer cells by targeting genes containing extended CUG TNRs required for cell survival [ 50 ].

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