BIOPHYSICAL THEORY AND MODELING |
Small RNAs Establish Delays and
Temporal Thresholds in Gene Expression
Stefan Legewie 1*, Dennis Dienst 2, Annegret Wilde 2, Hanspeter Herzel 3 and Ilka Axmann 3
1 Humboldt University
2 Humboldt University Berlin, Institute of Biology,
3 Humboldt University Berlin, Institute of Theoretical Biology,
* To whom correspondence should be addressed. E-mail: s.legewie{at}biologie.hu-berlin.de.
Submitted on March 18, 2008
Revised on April 14, 2008
Accepted on 18 June 2008
 |
Abstract |
|---|
Non-coding RNAs are crucial regulators of gene expression in prokaryotes and eukaryotes,
but it remains poorly understood how they affect the dynamics of transcriptional networks.
We analyzed the temporal characteristics of the cyanobacterial iron stress response by
mathematical modeling and quantitative experimental analyses, and focused on the role of a
recently discovered small non-coding RNA, IsrR. We found that IsrR is responsible for a
pronounced delay in the accumulation of isiA mRNA encoding the late-phase stress protein,
IsiA, and that it ensures a rapid decline in isiA levels once external stress triggers are
removed. These kinetic properties allow the system to selectively respond to sustained (as
opposed to transient) stimuli, and thus establish a temporal threshold, which prevents
energetically costly IsiA accumulation under short-term stress conditions. Biological
information is frequently encoded in the quantitative aspects of intracellular signals (e.g.,
amplitude and duration). Our simulations reveal that competitive inhibition and regulated
degradation allow intracellular regulatory networks to efficiently discriminate between
transient and sustained inputs.
Key Words:
competitive inhibition, delay, regulated degradation, signal duration, switch
