The understanding that mRNA degradation is critical for gene expression traces back to 1959 when Pardee Jacob and Monod demonstrated in a historical paper that there had to be an unstable intermediate directing protein synthesis. More recently, the spectacular use of RNAi to experimentally degrade specific mRNAs has expanded the applications of understanding mRNA decay mechanisms beyond any expectations. Thus, mRNA degradation is clearly of fundamental importance to gene expression, and a complete understanding of mRNA degradation mechanisms and its regulation has clear applications for understanding biomedical problems and for generating new tools for biomedical research. The FASEB meeting on mechanisms of mRNA decay has developed into a unique conference that brings together the leading experts in mRNA decay in metazoan, fungal, plant, bacterial, and archaeal systems. Although we have a thorough understanding of how transcription and its regulation contribute to gene expression, our understanding of post-transcriptional steps in gene expression is incomplete. Almost every iteration of this FASEB meeting has included revelations of new enzymes involved in mRNA decay, and more may remain to be discovered for the 2014 meeting. For example, at the last meeting in 2012 the first results that indicated that DIS3L2 was involved in mRNA decay were discussed. Thus, much remains to be discovered about the mechanism of mRNA degradation, and a complete understanding of the mechanism is an obvious pre-requisite to understanding regulation. Towards the broad and long-term goal of increasing our understanding of the mechanisms of mRNA degradation we are continuing a series of scientific meetings from July 6th to 11th 2014 in Big Sky, Montana. The 2014 meeting is the 9th in a series organized by FASEB, which followed similar meetings organized by ASM in the 90's. This series of meetings has had a major impact on the field and is exceptionally valued as evidenced by the fact that 96% of the attendees of the 2012 meeting indicated that they planned to attend the 2014 meeting on the evaluation form, that only 1 of the 36 invited speakers declined our invitation for the 2014 meeting, and by the enclosed support letters of session chairs for the upcoming meeting. We hope to achieve this goal through three specific aims
Public Health Relevance: Many human genetic diseases are caused by defects in mRNA degradation. Some of these diseases are caused by mutations that inactivate an mRNA decay enzyme or regulator. Other mutations change an mRNA and thereby how fast the mRNA is degraded. mRNA decay in bacterial pathogens is also important for their ability to cause infectious diseases.