Promoter architecture determines co-translational regulation of mRNA

Information that regulates gene expression is encoded throughout each gene but if different regulatory regions can be understood in isolation, or if they interact, is unknown. Here we measure mRNA levels for 10,000 open reading frames (ORFs) transcribed from either an inducible or constitutive promoter. We find that the strength of co-translational regulation on mRNA levels is determined by promoter architecture. Using a novel computational-genetic screen of 6402 RNA-seq experiments we identify the RNA helicase Dbp2 as the mechanism by which co-translational regulation is reduced specifically for inducible promoters. Finally, we find that for constitutive genes, but not inducible genes, most of the information encoding regulation of mRNA levels in response to changes in growth rate is encoded in the ORF and not in the promoter. Thus the ORF sequence is a major regulator of gene expression, and a non-linear interaction between promoters and ORFs determines mRNA levels.