mRNA turnover plays an essential role in gene expression. Specific cell signals can transiently stabilize unstable mRNAs or destabilize stable mRNAs to regulate protein expression. Misregulation of mRNA turnover is associated with a range of human diseases. Two important mRNA decay processes are those of nonsense-mediated decay (NMD), a process that detects and degrades mRNAs that fail to encode full-length protein, and AU-rich element (ARE)-mediated decay, which is responsible for the rapid decay of mRNAs with AREs. These are often found in the 3'UTR of mRNAs encoding proto-oncogenes, cytokines and growth factors. Both of these mRNA decay pathways trigger rapid mRNA deadenylation, an important often regulatory step in mRNA decay. With the long-term goal of understanding how mRNA decay is regulated in gene expression and disease, we have identified ten putative human deadenylases using a bioinformatics approach. These will be studied by: 1) testing their in vitro deadenylation activity, and 2) by studying their role in nonsense-mediated decay and in 3) ARE-mediated decay in human tissue culture cells.
