The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer.
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| Abstract |
We show here that under physiologically reasonable conditions, CGG repeats in RNA readily form hairpins. In contrast to its DNA counterpart that forms a complex mixture of hairpins and tetraplexes, r(CGG)22 forms a single stable hairpin with no evidence for any other folded structure even at low pH. RNA with the sequence (CGG)9AGG (CGG)12AGG(CGG)97, found in a fragile X syndrome pre-mutation allele, forms a number of different hairpins. The most prominent hairpin forms in the 3' part of the repeat and involves the 97 uninterrupted CGG repeats. In contrast to the CUG-RNA hairpins formed by myotonic dystrophy type 1 repeats, we found no evidence that CGG-RNA hairpins activate PKR, the interferon-inducible protein kinase that is activated by a wide range of double-stranded RNAs. However, we do show that the CGG-RNA is digested, albeit inefficiently, by the human Dicer enzyme, a step central to the RNA interference effect on gene expression. These data provide clues to the basis of the toxic effect of CGG-RNA that is thought to occur in fragile X pre-mutation carriers. In addition, RNA hairpins may also account for the stalling of the 40S ribosomal subunit that is thought to contribute to the translation deficit in fragile X pre-mutation and full mutation alleles.
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| Authors | Vaishali Handa, Tapas Saha, Karen Usdin |
| Journal | Nucleic acids research (Nucleic Acids Res) Vol. 31 Issue 21 Pg. 6243-8 (Nov 01 2003) ISSN: 1362-4962 [Electronic] England |
| PMID | 14576312 (Publication Type: Journal Article) |
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