The Shyu lab has a long-standing interest in understanding the principles and regulatory mechanisms that govern the cytoplasmic fate of messenger RNA (mRNA) in mammalian cells. These post-transcriptional processes (including mRNA turnover, translation, and localization) play an essential role in modulation and quality control of gene expression, and when they go awry, they can contribute to the pathogenesis of human disease such as cancer and airway inflammation. We have been using molecular, biochemical, cellular, and computational biology approaches, including next-generation sequencing-based methodologies combined with in-depth bioinformatics analysis to study the regulation of these critical processes in mammalian cells. We are applying/developing transcriptome-based metabolic pulse-chase labeling and RNA-IP approaches that allow better characterization of changes in global mRNA turnover caused by specific cellular events. Currently, we focus on investigating 1) how rates of mRNA decay may be coordinated for groups of mRNAs during cell growth and differentiation, and 2) the mechanisms by which global mRNA turnover shapes or reprograms the overall mRNA expression profile or transcriptome in mammalian cells responding to intra- or extra-cellular stimuli.