Abstract
The Cdk8 kinase module (CKM), a conserved, detachable unit of the Mediator complex, plays a vital role in regulating transcription and communicating stress signals from the nucleus to other organelles. Here, we describe a new transcription-independent role for Med13, a CKM scaffold protein, following nitrogen starvation. In Saccharomyces cerevisiae, nitrogen starvation triggers Med13 to translocate to the cytoplasm. This stress also induces the assembly of conserved membraneless condensates called processing bodies (P-bodies) that dynamically sequester translationally inactive messenger ribonucleoprotein particles. Cytosolic Med13 colocalizes with P-bodies, where it helps recruit Edc3, a highly conserved decapping activator and P-body assembly factor, into these conserved ribonucleoprotein granules. Moreover, Med13 orchestrates the autophagic degradation of Edc3 through a selective cargo-hitchhiking autophagy pathway that utilizes Ksp1 as its autophagic receptor protein. In contrast, the autophagic degradation of Xrn1, another conserved P-body assembly factor, is Med13 independent. These results place Med13 as a new player in P-body assembly and regulation following nitrogen starvation. They support a model in which Med13 acts as a conduit between P-bodies and phagophores, two condensates that use liquid-liquid phase separation in their assembly.