Abstract: Modulating the rate of mRNA degradation is a fast and efficient way to control gene expression. In a yeast strain deleted of EDC3, a component of the decapping machinery conserved in eukaryotes, the transcript coding the ribosomal protein Rps28b is specifically stabilized, as demonstrated by microarray and time course experiments. This stabilization results from the loss of RPS28B autoregulation, which occurs at the level of mRNA decay. Using mutants of the major deadenylase, we show that this regulation occurs at the level of decapping and bypasses deadenylation. Rps28b interacts with a conserved hairpin structure within the 3'UTR of its own mRNA and with components of the decapping machinery, including Edc3. We conclude that Rps28b, in the presence of Edc3, directly recruits the decapping machinery on its own mRNA. These findings show that specific modulation of the decapping efficiency on natural transcripts can control mRNA turnover.