Espinar, LorenaSchikora Tamarit, Miquel ÀngelDomingo Espinós, Júlia, 1991-Carey, Lucas, 1980-2018-12-122018-12-122018Espinar L, Schikora Tamarit MÀ, Domingo J, Carey LB. Promoter architecture determines cotranslational regulation of mRNA. Genome Res. 2018;28(4):509-18. DOI: 10.1101/gr.230458.1171088-9051http://hdl.handle.net/10230/36039Information 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 cotranslational regulation on mRNA levels is determined by promoter architecture. By using a novel computational genetic screen of 6402 RNA-seq experiments, we identify the RNA helicase Dbp2 as the mechanism by which cotranslational 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 nonlinear interaction between promoters and ORFs determines mRNA levels.application/pdfeng© 2018 Espinar et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1101/gr.230458.117info:eu-repo/semantics/openAccess