Coupled pre-mRNA and mRNA dynamics unveil the operation strategies underlying transcriptional responses

Transcriptional responses to stimuli are regulated by tuning rates of transcript production and degradation. Here we show that stimulation-induced changes in transcript production and degradation rates can be inferred from simultaneously measured precursor mRNA (pre-mRNA) and mature mRNA profiles. Our studies on the transcriptome-wide responses to extracellular stimuli in different cellular model systems revealed hitherto unanticipated dynamics of transcript production and degradation rates. Intriguingly, genes with similar mRNA profiles often exhibit marked differences in the amplitude and onset of their production. Moreover, we identify a group of genes, which take advantage of the unexpectedly large dynamic range of production rates to expedite their induction by a transient production overshoot. These findings provide an unprecedented quantitative view on processes governing transcriptional responses, and may have broad implications for understanding their regulation at the transcriptional and post-transcriptional levels.

21

Zeisel A, Köstler WJ, Molotski N, Tsai JM, Krauthgamer R, Jacob-Hirsch J, Rechavi G, Soen Y, Jung S, Yarden Y, Domany E