Castilla-Llorente et al. identify a protein that determines the localization and fate of miRNA-targeted mRNAs.
miRNAs silence their target mRNAs by incorporating them into silencing complexes (miRISCs) that contain members of the Argonaute and GW families of proteins. Once inside an miRISC, an mRNA can be translationally repressed or permanently degraded, but how these alternative fates are coordinated is unclear. Castilla-Llorente et al. shed light on this question when they identified a unique GW protein splice variant called GW220.
GW proteins have been associated with the formation of cytoplasmic ribonucleoprotein granules called P bodies, but Castilla-Llorente et al. found that not all P bodies contain GW proteins. Instead, GW220 localized to a distinct class of P bodies that also contained Argonaute proteins and miRNA-targeted mRNAs. These “GW/P bodies” were much more stable than other P bodies, suggesting that they might have a role in mRNA storage.
Overexpressing GW220 promoted GW/P body aggregation, whereas GW220 depletion reduced the formation of these granules. miRNAs suppressed protein expression in cells containing numerous GW/P bodies, but the target mRNA itself was fairly stable. In cells lacking GW/P bodies, however, miRNAs induced degradation of their target mRNAs.
GW220 therefore directs silenced mRNAs into GW/P bodies, where they are translationally repressed but protected from degradation. Senior author Jidong Liu now wants to identify additional RNA and protein components of GW/P bodies in order to determine the factors that regulate their formation and to establish which endogenous mRNAs are silenced within these granules.