Conformational Dynamics of hAgo2 Silencing: Decoding Functional Divergence across Human Argonaute Paralogs.

ABSTRACT: RNA interference (RNAi) is a key mechanism for controlling gene expression, with Argonaute (Ago) proteins serving as core effectors of the RNA-induced silencing complex (RISC). By loading small noncoding RNAs, Agos target complementary messanger RNAs (mRNAs), leading to their direct catalytic cleavage or the activation of translational repression. Among the four human Ago isoforms (hAgo1-4), only hAgo2 exhibits catalytic activity, a feature not fully explained by structural differences alone. This study explores the structural and functional distinctions among hAgo isoforms, both in their unbound and bound states, using miRNA-20a as a model system. Microsecond-scale molecular dynamics (MD) simulations reveal insightful differences in structural flexibility and plasticity. Catalytically act

SUBMITTER: Paladino A 

PROVIDER: S-EPMC12458702 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature