Coupled pre-mRNA and mRNA dynamics unveil operational strategies underlying transcriptional responses to stimuli

Mol Syst Biol. 2011 Sep 13:7:529. doi: 10.1038/msb.2011.62.

Abstract

Transcriptional responses to extracellular stimuli involve tuning the rates of transcript production and degradation. Here, we show that the time-dependent profiles of these rates can be inferred from simultaneous measurements of precursor mRNA (pre-mRNA) and mature mRNA profiles. Transcriptome-wide measurements demonstrate that genes with similar mRNA profiles often exhibit marked differences in the amplitude and onset of their production rate. The latter is characterized by a large dynamic range, with a group of genes exhibiting an unexpectedly strong transient production overshoot, thereby accelerating their induction and, when combined with time-dependent degradation, shaping transient responses with precise timing and amplitude.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Animals
  • Cell Line
  • DNA Probes / analysis
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Female
  • Genomics*
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / drug effects
  • Mammary Glands, Human / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Statistical
  • RNA Precursors* / genetics
  • RNA Precursors* / metabolism
  • RNA Stability*
  • RNA, Messenger* / biosynthesis
  • RNA, Messenger* / genetics
  • Real-Time Polymerase Chain Reaction
  • Stimulation, Chemical
  • Time Factors
  • Transcription, Genetic*
  • Transcriptome / genetics*

Substances

  • DNA Probes
  • Lipopolysaccharides
  • RNA Precursors
  • RNA, Messenger
  • Epidermal Growth Factor