Ancestral roles of small RNAs: an Ago-centric perspective - PubMed (original) (raw)

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Ancestral roles of small RNAs: an Ago-centric perspective

Leemor Joshua-Tor et al. Cold Spring Harb Perspect Biol. 2011.

Abstract

RNAi has existed at least since the divergence of prokaryotes and eukaryotes. This collection of pathways responds to a diversity of "abberant" RNAs and generally silences or eliminates genes sharing sequence content with the silencing trigger. In the canonical pathway, double-stranded RNAs are processed into small RNAs, which guide effector complexes to their targets by complementary base pairing. Many alternative routes from silencing trigger to small RNA are continuously being uncovered. Though the triggers of the pathway and the mechanisms of small RNA production are many, all RNAi-related mechanisms share Argonaute proteins as the heart of their effector complexes. These can act as self-contained silencing machines, binding directly to small RNAs, carrying out homology-based target recognition, and in some cases cleaving targets using an endogenous nuclease domain. Here, we discuss the diversity of Argonaute proteins from a structural and functional perspective.

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Figures

Figure 1.

Figure 1.

The three clades of the Argonautes. The Ago-like clade, shown in black, is based on similarity to AtAgo1; the Piwi-like clade, shown in green based on similarity to DmPiwi and the Wago's, which is a worm-specific clade is shown in red. Argonautes that contain a complete catalytic motif are underlined (Adapted from Tolia and Joshua-Tor 2007).

Figure 2.

Figure 2.

The crystal structure of Argonaute from P. furiosus shown as a ribbon diagram. The amino-terminal domain is in blue, the PAZ domain is red, the middle domain is green, and the PIWI domain is in purple. The interdomain connector is shown in yellow. A close-up of the active site residues coordinating a Mn++ ion (pink ball) is shown in the inset.

Figure 3.

Figure 3.

The crystal structure of Argonaute from Thermus thermophilus in complex with a 21-nucleotide DNA guide (in stick with gray carbons) and a 12-nucleotide RNA target (in stick with yellow carbons). The amino-terminal domain is in blue, the PAZ domain in red, the mid domain in green and the PIWI domain in purple. The two linkers are shown in gray. The first 12 nucleotides and the two 3′-nucleotides of the DNA guide are observed in the structure. The 3′ nucleotides are bound to the PAZ domain.

Figure 4.

Figure 4.

The crystal structure of Argonaute from T. thermophilus in complex with a 21-nucleotide DNA guide (in stick with gray carbons) and a 19-nucleotide RNA target (in stick with yellow carbons). Domains are colored as in Figure 3. The first 16 nucleotides of the DNA guide and 15 nucleotides of the RNA target strand are observed in the structure. The 3′-end nucleotides of the guide are no longer bound to the PAZ domain in this structure.

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