Sara Hanley Rowan Graduate School of Biomedical Sciences Stratford, New Jersey
In response to stress, cells rapidly adjust gene expression, translation, and protein levels to mitigate damage and initiate repair pathways. The Cdk8 Kinase Module (CKM) is a highly conserved, detachable unit of the Mediator complex that plays a vital role in regulating transcription and communicating stress signals from the nucleus to other organelles. Previously, our laboratory has shown that the scaffold protein within the CKM, Med13, is exported from the nucleus and degraded via a selective autophagy pathway following nitrogen starvation. In periods of starvation, cells attenuate translation and biosynthetic pathways to reserve nutrient pools. To rapidly adapt to starvation, cytosolic ribonucleoprotein (RNP) granules such as processing bodies (P-bodies) tightly regulate mRNA accessibility and translation. Here we show that Med13 plays a dual role in promoting P-body assembly. In physiological conditions, Med13 functions as a positive transcriptional regulator of P-body formation as the deletion of MED13 significantly decreases the quantity of P-bodies. In addition, during stress Med13 co-localizes with the P-body marker, Edc3, suggesting that Med13 may also play a scaffolding role within these membrane-less organelles. Taken together, these data demonstrate the duality of Med13 as a transcriptional regulator of P-bodies in unstressed conditions and a scaffolding component during stress. The nutrient sensing kinase, Ksp1, plays an important role in mediating P-body localization of Med13 and other mRNA binding proteins following nitrogen starvation. These data demonstrate a novel cytosolic role for Med13 and expand the known proteome of P-bodies.
