On the role of RNA amplification in dsRNA-triggered gene silencing.
basic_science · Level V
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Abstract
We have investigated the role of trigger RNA amplification during RNA interference (RNAi) in Caenorhabditis elegans. Analysis of small interfering RNAs (siRNAs) produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA. Instead, a population of siRNAs (termed secondary siRNAs) appeared to derive from the action of a cellular RNA-directed RNA polymerase (RdRP) on mRNAs that are being targeted by the RNAi mechanism. The distribution of secondary siRNAs exhibited a distinct polarity (5'-->3' on the antisense strand), suggesting a cyclic amplification process in which RdRP is primed by existing siRNAs. This amplification mechanism substantially augments the potency of RNAi-based surveillance, while ensuring that the RNAi machinery will focus on expressed mRNAs.
Medical subject headings
- Bacterial Proteins
- Caenorhabditis elegans
- Gene Silencing
- Helminth Proteins
- Models, Genetic
- RNA, Double-Stranded
- RNA, Helminth
- RNA, Untranslated
- RNA-Directed DNA Polymerase
- Transcription Factors