We are requesting partial support for a FASEB Conference on "post-transcriptional regulation of gene expression: mechanisms of mRNA decay" to be held in Tucson AZ on June 26-July 1, 2004. Turnover of mRNA is a key, but frequently unrecognized, regulator of gene expression as the stability of an mRNA dictates its ultimate steady-state level. Moreover, programmed instability is an important mechanism of repressing gene expression. In addition, it is increasingly recognized that most organisms employ means of surveillance of mRNA quality to ensure that only "fit" transcripts exit the nucleus and are translated. Targeted mRNA turnover is integral to this process. Finally, newly discovered means of antisense regulation, including RNA interference, rely on selective mRNA turnover for their biological consequences. For these reasons, mRNA turnover is attracting heightened interest from all areas of the life sciences. The proposed FASEB conference is unique in concentrating on mRNA decay, thereby exploring in diverse biological settings the mechanisms, both at the cellular and molecular levels, that underpin this universal process. The proposed meeting is particularly noteworthy in attracting investigators who study pro- and eukaryotic organisms and in focussing on mechanisms by which RNAs interact with the decay apparatus and the factors which modulate decay. The first third of the conference will explore the latest developments in our understanding of how the enzymes of mRNA decay initially interact with their targets. Such interactions largely occur at the ends of RNAs, often involving highly conserved proteins or protein complexes, but with many surprising twists. We anticipate that much needed structural investigations of these interactions will come to fruition and be presented for the first time at the proposed conference. The second portion of the conference will focus on the complex interactions among nascent mRNAs, the degradative machinery, nuclear export, quality control and translation. Understanding these processes and their interplay has myriad implications for regulation of growth, development, and disease. The final portion of the conference will focus on mechanisms of RNA interference (as opposed to the phenomenology) and the application of global approaches to understanding mRNA decay and its impact on whole cells. The conference will provide a superb overview of the latest progress in an exciting field and will propel the next stage of its development.