ABSTRACT
In mammalian cells, nonsense-mediated mRNA decay (NMD) degrades mRNAs that terminate translation sufficiently upstream of a post-splicing exon junction complex (EJC) of proteins. Components o f the EJC include the NM D factor Upfl. We have found that Upfl also interacts with the RNA binding protein Staufen (Stau) 1. To understand the significance of this finding, microarray analyses were used to identify mRNAs that bind Staul. For those mRNAs tested, Staul interacts with the 3 ’ untranslated region, and down-regulating the cellular level of Staul or Upfl increases mRNA half-life. These and other results indicate that Staul mediates the decay of specific cellular mRNAs when translation terminates nor mally. This Staul-mediated mRNA decay (SMD) contributes significandy to the network of post-transcriptional regulatory pathways in mammalian cells. SMD differs from NM D because it occurs independendy of splicing and after down-regulating Upf NM D factors other than Upfl. However, SMD is similar to NM D because it requires translation and the recruit ment o f U pfl sufficiently downstream of a termination codon.
