They found that Upf1 grabbed onto Staufen1 (Stau1). Stau1 is a well-known RNA binding protein and some of its functions in the common fruit fly Drosophila are understood. "But no one knew what Staufen1 did in human cells," said Maquat, even though its presence in mammalian cells has been recognized for several years.
"We were surprised to find that Staufen1 interacts with Upf1," she added. "This is a whole new function for Staufen1 that couldn't have been predicted from the studies in flies, even though a similar function may occur in flies."
The team discovered that Staufen1 doesn't interact with other components of the NMD complex ?and altering the amount of Staufen1 in the cell didn't change NMD function. Those observations, said Maquat, sent Kim on a hunt for what Staufen1 and Upf1 were doing.
Looking at gene expression data available through the lab of Luc DesGroseillers, Ph.D. at the University of Montreal, they found that Staufen1 protein binds to numerous RNAs. Downregulating the amount of Staufen or Upf1 increased the half-life of these RNAs. Significantly, altering the amount of another NMD factor didn't affect these RNAs.
Thus, Staufen1 and Upf1, together, degrade RNAs by a previously undescribed mechanism, which the team called Staufen1-mediated degradation (SMD). Preliminary results suggest that SMD activity affects numerous transcripts and, therefore, is a novel mechanism of gene regulation.
"We don't yet understand how SMD is regulated but it must be," said Maquat. "Both Upf1 and Staufen1 can be phosphorylated, so their activities could be regulated by cell signaling pathways, such as those mediated by changes in growth conditions." That would allow the cell to differentially control the level of SMD-target RN
Source:University of Rochester Medical Center