Two novel aspects of the kinetics of gene expression including miRNAs

Abstract

Abstract:In eukaryotic cells, many genes are transcribed into non-coding RNAs. Small RNAs or, more specifically, microRNAs (miRNAs) form an abundant sub-class of such RNAs. miRNAs are transcribed as long noncoding RNA and then generated via a processing pathway down to the 20-24-nucleotide length. The key ability of miRNAs is to associate with target mRNAs and to suppress their translation and/or facilitate degradation. Using the mean-field kinetic equations and Monte Carlo simulations, we analyze two aspects of this interplay. First, we describe the situation when the formation of mRNA or miRNA is periodically modulated by a transcription factor which itself is not perturbed by these species. Depending on the ratio between the mRNA and miRNA formation rates, the corresponding induced periodic kinetics are shown to be either nearly harmonic or shaped as anti-phase pulses. The second part of the work is related to recent experimental studies indicating that differentiation of stem cells often involves changes in gene transcription into miRNAs and/or the interference between miRNAs, mRNAs and proteins. In particular, the regulatory protein obtained via mRNA translation may suppress the miRNA formation, and the latter may suppress in turn the miRNA-mRNA association and degradation. The corresponding bistable kinetics are described in detail.

Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28

“…Nonlinear phenomena of the interplay among noncoding RNA (ncRNA), mRNA and protein in cellular systems have been intensively investigated primarily through the study of a recurrent network motif mediated by ncRNAs [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. These studies on the minimal architectures mediated by ncRNAs would greatly facilitate us to analyze complex systems assembled by these simple modules.…”