Gene regulation by synergism between mRNA decay and gene transcription

Abstract

It has become increasingly clear in the last few years that gene expression in eukaryotes is not a linear process starting from transcription in the nucleus to the cytoplasm, but a circular one where the mRNA level is controlled by crosstalk between nuclear transcription and cytoplasmic decay pathways. One of the possible purposes of this crosstalk is to keep the mRNA level approximately constant. This is called mRNA buffering and happens when transcription and mRNA degradation act at compensatory rates. However, if transcription and mRNA degradation act synergistically, enhanced gene expression regulation would occur. In this work we mathematically modeled the effects of RNA binding proteins (RBP) when they have positive or negative effects on mRNA synthesis and decay rates. We found that they can buffer or enhance gene expression responses depending on their respective effects on transcription and mRNA stability. Then we analyzed new and previously published genomic datasets obtained for several yeast mutants related to either transcription or mRNA decay, but they are not known to possess activity in the other process. We show that some of them, which were presumed only transcription factors (Sfp1) or only decay factors (Puf3, Upf2/3), may represent examples of RBPs that make specific synergistic crosstalk to enhance the control of the mRNA levels of their target genes by combining antagonistic effects on transcriptional and mRNA stability.