Mechanism of r(CUG)exp-containing intron 3 decay in FECD cells. (A) Effect of the siRNA targeting XRN1 in combination with 2b on TCF4 intron 3 levels, as determined by RT-qPCR. Knock-down of XRN1 had no effect on TCF4 intron 3 decay induced by 2b (n = 3). (B) Effect of the siRNA targeting hRRP6 in combination with 2b on TCF4 intron 3 levels, as determined by RT-qPCR (n = 3). Knock-down of hRRP6, a catalytic domain of the exosome complex, decreased TCF4 intron 3 decay generated by 2b. (C) Effect of the siRNA targeting hRRP44 in combination with 2b on TCF4 intron 3 levels, as determined by RT-qPCR (n = 3). Knock-down of hRRP44, a second catalytic domain of the exosome complex, decreased TCF4 intron 3 decay generated by 2b. (D) Proposed decay mechanism, where the exosome complex plays a key role in the decay pathway. Exosome nucleolytic domains are represented in orange including the hRRP6 and hRRP44 subunits. Data are represented as mean ± SD. *P, < 0.05; **P, < 0.01, as determined by a two-tailed Student t-test. See also Figure S6.