Thursday, 7 April 2011

Hello, I Must Be Going

Lara Szewczak and Brian Plosky

Messenger RNAs are largely of low abundance with limited lifetimes. Combating the experimental challenge of measuring RNAs in living cells, Miller et al. (2011) apply a combination of experimental and computational approaches to look at mRNA synthesis and decay in yeast with minimal perturbations to the cells. The trick, which has been previously applied in cells from other organisms, is to induce the cells to incorporate a nucleoside analog, 4-thiouridine, to enable selective isolation of newly synthesized transcripts. Microarray analysis of the selected mRNAs from more than 4000 yeast genes enables quantitative analysis of mRNA synthesis over time, and this information, coupled with decay rates, provides a cellular view on the dynamics of mRNA biogenesis and stability. The results confirm the general idea that most mRNAs are fleeting members of the cellular community, with only a few copies of each mRNA being made in a given cell cycle. The authors also find that transcription and decay can recur for a given sequence repeatedly during the cell cycle. Not unexpectedly, the two processes are uncoupled under basal conditions. However, the pattern changes during a stress response. For example, osmotic shock leads to a transient coregulation between the processes. During the first stage of the cellular response, both mRNA synthesis and decay are repressed as the cells hunker down to protect the resources that they have, followed by a increase in both synthesis and decay as response genes ride to the rescue in a short-term response and are then hustled away to make way for a return to homeostasis. Analysis of these cell-wide patterns also highlights new factors that are involved in the osmotic stress response and suggests candidate protein-protein interactions between transcription factors driving the response. The general utility of the approach will pave the way for similar analyses in diverse cell types, enabling a fine-scale dissection of mRNA dynamics in response to a variety of conditions.
Miller, C., et al. (2011). Mol. Syst. Biol. 7, 458.