Lal Ashish, Gorospe Myriam
Laboratory of Cellular and Molecular Biology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Cell Cycle. 2006 Jul;5(13):1422-5. doi: 10.4161/cc.5.13.2902. Epub 2006 Jul 1.
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.
尽管转录在历史上占据主导地位，但越来越多的证据支持通过mRNA剪接、定位、周转和翻译等过程进行转录后基因调控的重要性。然而，这些步骤中的每一个在很大程度上仍被视为一个独立的命题，即在特定情况下，一个特定基因由单一的特定调控机制控制。我们最近对gadd45a在基因毒性应激反应中的表达进行的研究表明了一种更为复杂的情况，其中转录变化与mRNA周转和翻译调控协同作用。因此，gadd45a加入了少数已报道的基因行列，这些基因的水平通过DNA和RNA结合蛋白的协同作用，在细胞损伤或有丝分裂信号的作用下发生显著改变。通过作用于不同水平的多种因素进行基因调控，引发强烈、迅速且多样的细胞反应，正成为越来越多对细胞稳态至关重要的基因产物的常态，而非例外。
