Mechanisms of RNAi: mRNA cleavage fragments may indicate stalled RISC

Review Article

J RNAi Gene Silenc (August 2005), 1(1), 21-25

doi: jrgsxx

Published online: 28 July 2005

Full Text: (html | pdf ~697kb | refs)

Mechanisms of RNAi: mRNA cleavage fragments may indicate stalled RISC

Torgeir Holen

Centre for Molecular Biology and Neuroscience (CMBN), University of Oslo, Norway

Correspondence to: Torgeir Holen, Email: torgeir.holen@basalmed.uio.no, Tel: +47 2285 1018, Fax: +47 22851488

Received:26 April 2005, Revised: 15 May 2005, Accepted: 18 May 2005

© Copyright The Author

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ABSTRACT

The molecular mechanism of RNA interference (RNAi) is under intense investigation . We previously demonstrated the existence of inactive siRNAs and also of mRNA cleavage in vivo in human cells. Here it is shown that some siRNAs with low activity leave mRNA cleavage fragments while an siRNA with higher activity does not. The pattern is consistent with both short-term (4-24 hours) and long-term (1-4 days) time-series. Analysis of the putative 3’ mRNA cleavage product showed high GC content immediately after the cleavage point. The cleavage fragments might indicate a stalled or slowed RNAi cleavage complex – possibly in the RISC enzyme restoration phase – and thus constitute a novel explanation for the existence of inactive siRNAs.

KEYWORDS: RNAi, RISC, siRNA, activity, mechanism

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