Structural and functional insights into eukaryotic mRNA decapping

The control of messenger RNA (mRNA) translation and degradation is important in regulation of eukaryotic gene expression. In the general and specialized mRNA decay pathways which involve 5(') →3(') decay, decapping is the central step because it is the controlling gate preceding the actual degradation of mRNA and is a site of numerous control inputs. Removal of the cap structure is catalyzed by a decapping holoenzyme composed of the catalytic Dcp2 subunit and the coactivator Dcp1. Decapping is regulated by decapping activators and inhibitors. Recent structural and kinetics studies indicated that Dcp1 and the substrate RNA promote the closed form of the enzyme and the catalytic step of decapping is rate limiting and accelerated by Dcp1. The conformational change between the open and closed decapping enzyme is important for controlling decapping, and regulation of this transition has been proposed to be a checkpoint for determining the fate of mRNAs. Here we summarize the past and recent advances on the structural and functional studies of protein factors involved in regulating mRNA decapping.