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View the The Journal for Friday, March 7, 2025

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

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Mohamed et al. report the cryoelectron microscopy structure of human AGO2 with fully paired guide RNA. Their analysis reveals the structural basis for the slicing activity that drives RNAi, showing that the slicing-competent conformation is achieved by domain movements and RNA-protein contacts distinct from those of conformational intermediates and prokaryotic homologs.