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Suppression of RNA Silencing by Viruses

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Overview

Andrew Z. Fire and Craig C. Mello shared the 2006 Nobel Prize in Medicine or Physiology for their discovery of RNA interference - gene silencing by double-stranded RNA.

RNA interference (RNAi) (also known as post-transcriptional gene silencing (PTGS) or RNA silencing) is an evolutionarily conserved cellular response to the presence of double-stranded (ds) RNA that functions as a gene inactivation system in many eukaryotes and relies on tiny RNAs as the targeting molecules. One function of RNA silencing is to act in surveillance against molecular parasites, such as viruses, several of which rely on double-stranded RNA for replication. Viruses have developed mechanisms to counteract RNAi by providing proteins that sequester the tiny silencing RNAs (siRNAs) targeted against viral RNAs.

For a general introduction to RNA interference, see the pertinent section in Molecular Biology of the Cell by Alberts et al. or the Howard Hughes Medical Institute interactive online resource on the RNAi mechanism and overview of key scientific findings or an animation from Nature Publishing Group on the mechanism of RNA Interference.

Three structures, in particular, have provided insight into the basis for the molecular interactions involved in suppression of gene silencing (RNAi) by plant and animal viruses. Interestingly, the three proteins in these examples each employ a unique solution to bind the double stranded silencing RNA: one interacts with the major groove, one interacts mainly with the minor groove, and one uses "molecular calipers" to measure the size of the silecing RNA. In Proteopedia, there are separate detailed entries for each of these structures:

Carnation italian ringspot virus p19 bound to siRNA

Tomato aspermy virus protein 2b bound to siRNA

Flock house virus B2 protein bound to siRNA

 

 

Related Structures and Topics

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Wayne Decatur, David Canner

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