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Study provides insight into cellular defenses against genetic mutation

ich mRNAs pass muster as legitimate templates, and that sees to the destruction of the rest. They also found that the screening process, called nonsense-mediated mRNA decay (NMD), can nearly eliminate the supply of an mRNA template for an essential protein because the mRNA has acquired a nonsense codon.

"Our study is important because we have determined for the first time that the mRNA-binding protein CBP80 tells the NMD system which mRNAs to review for nonsense codons," according to Lynne E. Maquat, Ph.D., professor of Biochemistry and Biophysics at the Medical Center, and senior author of the Nature piece together with post-doctoral associate Nao Hosoda, Ph.D. "That is critically significant because, knowing the structure and role of CBP80, we can now seek to develop drug-based gene therapies that interfere with it in cases where NMD contributes to disease-causing protein shortages." Researchers may be able to convert mRNA quality control from NMD over to a more flexible system that "overlooks" flaws, and provides more templates for building functional proteins.

Genetic Decision Maker

For two decades, researchers have made intuitive leaps in the understanding how NMD works with translation, the second phase of gene expression where RNAs direct the building of proteins. From studying genetic diseases, Maquat theorized four years ago that there must be two types of translation. An early "pioneer" round checks all new mRNAs for errors, and initiates NMD when errors are detected. A second "steady-state" round translation then directs the mass production of normal proteins based on "NMD-approved" mRNAs. Recently, Maquat's team has worked to identify the roles of proteins involved in NMD, the focus of the Nature paper.

During translation, mRNA chains are read in one direction due to the nature of their building blocks, called nucleotides, starting with the 5-prime end, and ending with the 3-prime end. As mRNA chains are synthe
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Source:University of Rochester Medical Center


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