Egad, more forms of gene regulation: the gadd45a story.

Despite the historical hegemony of transcription, mounting evidence supports the importance of posttranscriptional gene regulation via processes such as mRNA splicing, localization, turnover, and translation. However, each of these steps is still largely viewed as an exclusive proposition, whereby a particular gene under given circumstances is controlled by a single specific regulatory mechanism. Our recent investigation of gadd45a expression in response to genotoxic stress illustrates a more complex scenario, wherein transcriptional changes operate in concert with mRNA turnover and translational regulation. gadd45a thus joins a handful of reported genes whose levels are potently altered in response to cellular damage or mitogenic cues through the coordinated action of DNA- and RNA-binding proteins. Eliciting cellular responses that are strong, swift, and versatile, gene regulation by multiple factors acting on different levels is emerging as the norm, rather than the exception, for a growing collection of gene products which critically influence cellular homeostasis.