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A new mechanism of regulating RNA degradation

As any dedicated video game player knows, the first requirement for using a weapon or tool is finding it. And it is no different for cell biologists and clinicians who want to take control of gene expression in cells to create therapies to treat disease. While cells have a variety of ways to control gene expression, the trick for players in this game is to recognize them amidst the incredibly complex background of cellular machinery.

Now, in a paper in the January 28th issue of Cell, Lynne E. Maquat, Ph.D., professor of Biochemistry and Biophysics at the University of Rochester Medical Center, and her team have identified a novel pathway for RNA degradation, a form of regulation that has garnered significant attention in recent years, and one that has the potential to produce a new set of tools for physicians to use to fight disease.

Most of the gene-control tools researchers have collected thus far involve the first step in gene expression, in which DNA is copied into RNA transcripts. However, recent discoveries have shown that many of the tools cells use to regulate genes work after transcription, by moderating the activity and the life span of the RNA itself.

One major pathway for such post-transcriptional regulation is called nonsense-mediated decay (NMD). Originally NMD was thought to destroy incorrectly transcribed or otherwise problematic RNAs, but investigators now know that it plays a major role in regulating the life span of numerous RNAs, and thus controls gene activity.

To better understand what controls the NMD system, Maquat and her postdoctoral fellow, Yoon Ki Kim, Ph.D., used a critical component of the NMD complex, Upf1, as bait in a molecular fishing expedition. With this approach, proteins that naturally interact with the bait will be pulled out of the pool of cellular proteins.

They found that Upf1 grabbed onto Staufen1 (Stau1). Stau1 is a well-known RNA binding protein and some of its functions in the
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Contact: Germaine Reinhardt
germaine_reinhardt@urmc.rochester.edu
585-275-6517
University of Rochester Medical Center
27-Jan-2005


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