The Timing Is in the Genes

Science Signaling  24 Feb 2009:
Vol. 2, Issue 59, pp. ec69
DOI: 10.1126/scisignal.259ec69

Tumor necrosis factor (TNF) activates transcription of genes required for immediate, medium-term, and long-term phases of inflammation. Hao and Baltimore examined the temporal order of genes that were induced in TNF-treated fibroblasts, cells that are usually present at the injury site, and found that they could group these genes according to time of peak mRNA expression. Expression of group I genes peaked early (0.5 hours), then declined to baseline quickly, whereas expression of group II genes rose steadily until 2 hours, and expression of group III genes gradually rose and peaked at 12 hours or later. Removal of TNF caused the abundance of mRNAs for group I genes to rapidly decrease and that of mRNAs for group II genes to plateau, whereas the mRNAs for group III genes remained stable, which suggests that mRNA stability determined the timing of gene activation. Indeed, differences in the temporal order of gene expression in TNF-treated macrophages compared with that in fibroblasts could be attributed to variations in mRNA half-life. mRNA stability appeared to be intrinsic to the genes, as it correlated in part with the number of adenine-uracil (AU)–rich elements (AREs) in the 3′ untranslated region (UTR): Group I genes contained the highest number of AREs (4 to 10), whereas group III genes had no AREs or 1 ARE. The authors and Anderson in the associated commentary note that genes with less stable mRNAs tended to function during acute phases of inflammation, with more stable mRNAs usually operating during later stages of inflammation.

S. Hao, D. Baltimore, The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat. Immunol. 10, 281–288 (2009). [PubMed]

P. Anderson, Intrinsic mRNA stability helps compose the inflammatory symphony. Nat. Immunol. 10, 233–234 (2009). [PubMed]