Telomeres Acquire Distinct Heterochromatin Characteristics during siRNA-Induced RNA Interference in Mouse Cells
| Autor: | Ho Keung Ng, Ava Kit Ying Yeung, Anthony W.I. Lo, Cecilia Yuen Sze Ho, John P. Murnane |
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| Rok vydání: | 2008 |
| Předmět: |
Heterochromatin
Biology General Biochemistry Genetics and Molecular Biology Cell Line Mice chemistry.chemical_compound RNA interference Animals RNA Small Interfering Gene Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) RNA DNA Fibroblasts Telomere Molecular biology RNA silencing chemistry RNA Interference General Agricultural and Biological Sciences Small nuclear RNA |
| Zdroj: | Current Biology. 18:183-187 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2007.12.059 |
| Popis: | SummaryTelomeres 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 nucleotides 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 1β (HP1β) 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 transgene 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 RNAi. |
| Databáze: | OpenAIRE |
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