Decapping Activators in Saccharomyces cerevisiae Act by Multiple Mechanisms

SummaryEukaryotic mRNA degradation often occurs in a process whereby translation initiation is inhibited and the mRNA is targeted for decapping. In yeast cells, Pat1, Scd6, Edc3, and Dhh1 all function to promote decapping by an unknown mechanism(s). We demonstrate that purified Scd6 and a region of Pat1 directly repress translation in vitro by limiting the formation of a stable 48S preinitiation complex. Moreover, while Pat1, Edc3, Dhh1, and Scd6 all bind the decapping enzyme, only Pat1 and Edc3 enhance its activity. We also identify numerous direct interactions between Pat1, Dcp1, Dcp2, Dhh1, Scd6, Edc3, Xrn1, and the Lsm1-7 complex. These observations identify three classes of decapping activators that function to directly repress translation initiation and/or stimulate Dcp1/2. Moreover, Pat1 is identified as critical in mRNA decay by first inhibiting translation initiation, then serving as a scaffold to recruit components of the decapping complex, and finally activating Dcp2.

► Pat1 activates decapping by repressing translation and stimulating Dcp2
► Scd6 and Dhh1 activate by repressing translation, while Edc3 enhances Dcp2 activity
► Both Pat1 and Scd6 inhibit a stable 48S initiation complex to repress translation
► Pat1 is a scaffold, interacts with the ribosome/translation repressors/decay factors