The study investigates the localization of microRNAs (miRNAs) and their target mRNAs to processing bodies (P-bodies) in mammalian cells. MiRNAs, which do not typically cleave target mRNAs, repress protein synthesis through mechanisms that are not well understood. The authors demonstrate that Argonaute proteins, key components of the RNA interference (RNAi) effector complex RISC, localize to P-bodies. They show that reporter mRNAs targeted for translational repression by endogenous or exogenous miRNAs accumulate in P-bodies in a miRNA-dependent manner. This suggests that miRNA-mediated translation repression delivers mRNAs to P-bodies, either as a cause or consequence of inhibiting protein synthesis. The study also reveals that the interaction between Argonaute proteins and P-body components, such as Dcp1a and Dcp2, is independent of ribonucleoprotein (RNP) or P-body integrity. Furthermore, the accumulation of Argonaute proteins in P-bodies requires their ability to bind miRNAs. The authors propose that miRNA-regulated mRNAs accumulate in P-bodies in conjunction with an Argonaute-miRNA complex, potentially explaining the connection between miRNA-mediated regulation and P-bodies.The study investigates the localization of microRNAs (miRNAs) and their target mRNAs to processing bodies (P-bodies) in mammalian cells. MiRNAs, which do not typically cleave target mRNAs, repress protein synthesis through mechanisms that are not well understood. The authors demonstrate that Argonaute proteins, key components of the RNA interference (RNAi) effector complex RISC, localize to P-bodies. They show that reporter mRNAs targeted for translational repression by endogenous or exogenous miRNAs accumulate in P-bodies in a miRNA-dependent manner. This suggests that miRNA-mediated translation repression delivers mRNAs to P-bodies, either as a cause or consequence of inhibiting protein synthesis. The study also reveals that the interaction between Argonaute proteins and P-body components, such as Dcp1a and Dcp2, is independent of ribonucleoprotein (RNP) or P-body integrity. Furthermore, the accumulation of Argonaute proteins in P-bodies requires their ability to bind miRNAs. The authors propose that miRNA-regulated mRNAs accumulate in P-bodies in conjunction with an Argonaute-miRNA complex, potentially explaining the connection between miRNA-mediated regulation and P-bodies.