Dcp2 C-terminal cis-binding elements control selective targeting of the decapping enzyme by forming distinct decapping complexes

A single Dcp1-Dcp2 decapping enzyme targets diverse classes of yeast mRNAs
for decapping-dependent 5’ to 3’ decay, but the molecular mechanisms
controlling selective mRNA targeting by the enzyme remain elusive. Through
extensive genetic analyses we uncover cis-regulatory elements in the Dcp2
C-terminal domain that control selective targeting of the decapping enzyme
by forming distinct decapping complexes. Two Upf1-binding motifs target
the decapping enzyme to NMD substrates, and a single Edc3-binding motif
targets both Edc3 and Dhh1 substrates. Pat1-binding leucine-rich motifs
target Edc3 and Dhh1 substrates under selective conditions. Although it
functions as a unique targeting component of specific complexes, Edc3 is a
common component of multiple complexes. Xrn1 also has a specific Dcp2
binding site, allowing it to be directly recruited to decapping complexes.
Collectively, our results demonstrate that Upf1, Edc3, and Pat1 function
as regulatory subunits of the holo-decapping enzyme, controlling both its
targeting specificity and enzymatic activation