Design of siRNAs Producing Unstructured Guide RNAs Results in Improved RNA Interference Efficiency  

Oleh:

Patzel, Volker ; Rutz, Sascha ; Dietrich, Isabell ; Koberle, Christian ; Scheffold, Alexander ; Kaufmann, Stefan H. E.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 11 (Nov. 2005), page 1440-1444.
Topik: rna; RNA; efficiency

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.4 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

In RNA interference (RNAi). Guide RNAs direct RNA-induced silencing complexes (RISC) to their mRNA targets, thus enabling the cleavage that leads to gene silencing. We describe strong inverse correlation between the degree of guide RNA secondary structure formation between the degree of guide RNA secondary structure formation and gene silencing by small interfering (si)RNA. Unstructure guide strands mediate the strongest sukencung whereas structures with base paired ends are inactive. Thus the availability of terminal nucleotides within guide structures determines the strength of silencing. A to G and C to U base exchanges, which involve wobble base pairing with the target but preserve complementarity, turned inactive into active guide structures, thereby expanding the space of functional siRNAs. Previously observed base degenerations among mature micro (mi) RNAs together with the data presented here suggest a crucial role of the guide-RNA structures in miRNA action. The analysis of the effect of the secondary structures of guide RNA sequences on RNAi efficiency provides a basis for better understanding RNA silencing pathways and improving the design of siRNAs.

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