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MicroRNA Conflict Resolution

08/01/2007

From the August 1 Issue of G&D
Embargoed until 5pm EST on 7.31:

MicroRNA Conflict Resolution: Experimental Recapitulation of miRNA-Mediated Repression

In the August 1st issue of G&D, a team of Japanese scientists led by Dr. Shigeyuki Yokoyama (RIKEN and the University of Tokyo), presents heretofore the most relevant experimental system of microRNA-mediated translational repression.

“Our cell-free system provides breakthrough in elucidating miRNP function,” according to Dr. Yokoyama.

Their study provides unprecedented insight into how miRNAs repress translation, and helps to resolve the current conflict over the precise mechanism of miRNA action.

Dr. Yokoyama and colleagues developed a cell-free system using extracts from human epithelial cells that were engineered to over-express specific miRNA pathway components. They introduced exogenous let-7 miRNAs and monitored its effects on the translation of luciferase reporter mRNA.

The researchers found that let-7 miRNAs recruited miRNP complexes containing Ago2 and GW182 proteins to target mRNAs, resulting in mRNA deadenylation and translational repression. These findings suggest that miRNAs interfere with the initiation step of translation.

Defining the Active Site of Bax


In the August 1st issue of G&D, scientists from the University of Nebraska Medical Center, led by Dr. Xu Luo, have identified the long-sought-after homo-oligomerization domain of Bax. The researchers demonstrate that the homo-oligomerization domain is, in fact, responsible for Bax’s apoptotic activity. Structural analysis revealed that a three-helix unit – consisting of helix 2 from the BH3 domain, and helices 4 and 5 from the BH1 domain – together form the homo-oligomerization domain. Dr. Luo and colleagues went on to show that this is the minimal domain required for the permeabilization of the mitochondrial membrane and the corresponding induction of apoptosis. "How activated Bax (or Bak) causes mitochondrial damage remains one of the most fascinating and important questions in apoptosis research. Establishing the causal relationship between homo-oligomerization and apoptotic activity of Bax and the identification of the Bax homo-oligomerization domain represent one step forward towards answering that question," explains Dr. Luo.

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Genes & Development
Cold Spring Harbor Laboratory
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