Telomeres acquire distinct heterochromatin characteristics during siRNA-induced RNA interference in mouse cells

Telomeres are protective structures present at the ends of linear chromosomes and consist of simple repeating-DNA sequences and specialized proteins [1, 2]. Integrity of the telomeres is important in maintaining genome stability (1-6]. RNA interference (RNAi) involves short double-stranded RNA (21-23 nucleoticles long), termed short interference RNA (siRNA), resulting in the downregulation of genes with cognate sequences [7-9]. During transient siRNA-induced RNAi in mouse fibroblast cultures, we found significant reversible changes related to the telomeres. Telomeres acquired distinct heterochromatin features. There were increased bindings of Argonaute-1 (AGO1), telomeric repeat-binding factor 1 (TERF1), and heterochromatin protein 1 beta (HP1 beta) on the telomeres. Histone H3 (lysine 9) was hypermethylated at the telomeres. The chromosome ends also were associated with an unidentified RNA. During RNAi, expression of a trans-gene inserted adjacent to the telomere was downregulated. In addition, the concentration of a group of heterogeneous high-molecular-weight RNA containing telomeric repeat sequences was increased, and this RNA formed a small number of transient, discrete nuclear foci. Our findings suggest that telomeres participate actively in the siRNA-induced RNAi process. These responses of telomeres to the RNAi process might partially account for the off-target effects of FINAL