A Piwi domain (part of RNAi protein argonaut)/siRNA-like duplex complex
RNA degradation is one of the mechanisms developed by organisms as a means of protection against foreign RNA molecules. RNA interference (RNAi) is a mechanism involving the cleavage of RNA. RNAi is also a powerful mechanism that can be used by scientists to turn off the expression of individual genes in a cell by degrading its mRNA. RNAi is triggered by the presence of double stranded RNA which is cleaved into smaller 20 nucleotide duplex strands called small interfering RNA (siRNA) by an enzyme called Dicer. siRNA then guide the RNA-induced silencing complex (RISC) or the RNA-induced initiation of transcriptional gene silencing (RITS) to mRNA targets for cleavage. RISC functions in post-transcriptional silencing, whereas RITS plays a role in transcriptional silencing. The mRNA targets degraded are those that are complementary to the siRNA. The Argonaut proteins are common to both the RISC and RITS complexes. They have a PIWI/Argonaut/Zwille (PAZ) domain at their amino-terminal and a PIWI domain at the carboxy-terminal. The PAZ domain recognizes the RNA 3A overhang of guide RNA. The PIWI domain incorporates the catalytic slicer site which cleaves the target mRNA.
The structure here is that of a Piwi protein from archaeoglobus fulgidus (AfPiwi) bound to a small siRNA like duplex in an L-shaped channel. The 5A end of the guide RNA is strongly bound to a highly conserved region I (CRI) in the PIWI domain, which also binds a divalent metal ion. The target strand has a few weak interactions with the PIWI domain as required for its dissociation after mRNA cleavage. The structure shows how the site-specificity of the target mRNA cleavage is determined with reference to the 5A end of the guide. Thus the Argonaut proteins interact with the 5A end and the 3A overhang of the short guide RNA through the PIWI domain and the Paz domain respectively, presenting them for the recognition of target mRNAs.
Protein Data Bank (PDB)
author: Ashwini Patil