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.

Mechanistic insights into mRNA export through structures of Dbp5.

Nuclear export of mRNA is a critical event in mRNA biogenesis. Passage of mature messenger ribonucleoproteins (mRNPs) through nuclear pore complexes (NPCs) is facilitated by the Mex67/Mtr2 heterodimer. At the NPC cytoplasmic face, the DEAD-box RNA helicase Dbp5 remodels mRNPs by removing Mex67/Mtr2.

Structural aspects of RNA helicases in eukaryotic mRNA decay.

mRNA decay is critical for the regulation of gene expression and the quality control of mRNA. RNA helicases play a key role in eukaryotic mRNA decay. In general, RNA helicases utilize the energy of ATP hydrolysis to remodel RNA or RNA-protein complexes, resulting in the separation of RNA duplex strand and/or displacement of proteins from the RNA molecule in RNP (ribonucleoprotein) complexes.

Crystal structure of human Edc3 and its functional implications.

Edc3 is an enhancer of decapping and serves as a scaffold that aggregates mRNA ribonucleoproteins together for P-body formation. Edc3 forms a network of interactions with the components of the mRNA decapping machinery and has a modular domain architecture consisting of an N-terminal Lsm domain, a central FDF domain, and a C-terminal YjeF-N domain. We have determined the crystal structure of the N-terminally truncated human Edc3 at a resolution of 2.

Sprouty 2, an inhibitor of mitogen-activated protein kinase signaling, is down-regulated in hepatocellular carcinoma.

The Sprouty proteins are increasingly being recognized to be deregulated in various types of cancers. This deregulation is often associated with aberrant signaling of receptor tyrosine kinases and its downstream effectors, leading to the mitogen-activated protein kinase (MAPK) signaling pathway. In human hepatocellular carcinoma, where the MAPK activity is enhanced via multiple hepatocarcinogenic factors, we observed a consistent reduced expression of the sprouty 2 (Spry2) transcript and protein in malignant hepatocytes compared with normal or cirrhotic hepatocytes.