Quantifying mRNA synthesis and decay rates using small RNAs.

Regulation of mRNA decay is a critical component of global cellular adaptation to changing environments. The corresponding changes in mRNA lifetimes can be coordinated with changes in mRNA transcription rates to fine-tune gene expression. Current approaches for measuring mRNA lifetimes can give rise to secondary effects due to transcription inhibition and require separate experiments to estimate changes in mRNA transcription rates. Here, we propose an approach for simultaneous determination of changes in mRNA transcription rate and lifetime using regulatory small RNAs (sRNAs) to control mRNA decay. We analyze a stochastic model for coupled degradation of mRNAs and sRNAs and derive exact results connecting RNA lifetimes and transcription rates to mean abundances. The results obtained are then generalized to include nonstoichiometric coupled degradation of sRNAs. Our analysis suggests experimental protocols for determining parameters controlling the efficiency of stoichiometric regulation by small RNAs and for analyzing factors and processes regulating changes in mRNA transcription and decay. (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.