AU-rich transient response transcripts in the human genome: expressed sequence tag clustering and gene discovery approach

Transient response genes regulate critical biological responses that include cell proliferation, signal transduction events, and responses to exogenous agents such as inflammatory stimuli, microbes, and radiation. An important feature that ensures a timely response is the short half-life of the messenger RNA (mRNA), which is thought to be predominantly mediated by adenylate uridylate-rich sequence elements (AREs) in the 3′ untranslated region (3′ UTR). The repertoire and extent of transient response genes in the human genome are not known. We used a computational approach to delineate those genes that code for transient ARE mRNAs. We utilized a 3′ UTR-specific ARE motif to retrieve and cluster 3′-end ESTs using a refined extraction protocol. With the availability of the entire human genome, we were able to utilize ARE EST clusters for further mining and computational prediction of ARE genes. The described approaches led to the finding of more than 1500 ARE genes in the human genome. In particular, “hidden” ARE mRNAs and alternative forms due to 3′UTR completeness, variant polyadenylation, and splicing were uncovered.