Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Poster Session I

17-POS Board 17 Short Linear Motifs and Activation of Dcp2-mediated mRNA Decapping Jeffrey S. Mugridge , John D. Gross. University of California, San Francisco, San Francisco, USA.

Cellular regulation of messenger RNA (mRNA) is crucial for proper gene expression. 5’-to-3’ mRNA decay is one of the major pathways used by eukaryotes to regulate mRNA levels and carry out mRNA quality control. A critical step in the 5’-to-3’ decay pathway is the removal of the protective methyl-guanosine cap found on the 5’-end of all eukaryotic mRNA, which commits the transcript to rapid degradation. Cleavage of the cap structure is catalyzed by the conserved decapping enzyme Dcp2, in combination with protein coactivators that modulate decapping activity. Many of these coactivators employ unstructured, short linear motifs to bind and activate the decapping enzyme. Dcp2 is a dynamic enzyme and one of the ways disordered motifs in coactivators may accelerate catalysis is by shifting Dcp2 conformational equilibria to promote the active conformation of the decapping complex. Here we present in vitro biophysical (NMR) and biochemical (enzymology) data characterizing Dcp2 function in the presence of disordered coactivator motifs. We propose a conserved model of Dcp2 activation in which short linear coactivator motifs contact Dcp2 near the active site and promote the active conformation of the decapping enzyme.

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