Nonsense-mediated mRNA decay goes to the spa: yeast(s) mechanisms, new RNA substrates and protein co-factors

Présentation

Abstract: One of the conserved pathways for RNA degradation in eukaryotes, NMD, is triggered by a translating ribosome that encounters a premature termination codon. This event is sensed by NMD factors, leading to degradation of the affected mRNA. One of the best studied NMD factor is the RNA helicase Upf1, an enzyme that physically interacts with two mutually exclusive sets of proteins. One of them contains Upf2 and Upf3, of unknown function, and the other is composed of factors that are involved in mRNA decapping or endonucleolytic cleavage, which initiate RNA degradation. Additional factors, such as the exonuclease Xrn1 or the 3' to 5' exosome complex, are required for removal of decapped RNA or RNA fragments. Our studies of NMD complexes in Saccharomyces cerevisiae uncovered a high level of conservation of the interactions that involve Upf1 and its co-factors, leading to new hypotheses about the evolution of NMD molecular mechanisms. Unexpectedly, we found that Upf1 is associated with thousands of mRNA that were not known to be NMD substrates and represent a short poly(A) (spa) fraction of cellular mRNAs. In the absence of NMD, spa mRNAs were stabilized, suggesting that NMD plays additional roles in RNA degradation. These results open new questions in the field about how an RNA helicase can specifically target only a fraction of mRNA based on the poly(A) tail length and how widespread this NMD-like mechanism is among other organisms.