title: Folding free energies of 5'-UTRs impact post-transcriptional regulation on a genomic scale in yeast.
abstract: Using high-throughput technologies, abundances and other features of genes and proteins have been measured on a genome-wide scale in Saccharomyces cerevisiae. In contrast, secondary structure in 5'-untranslated regions (UTRs) of mRNA has only been investigated for a limited number of genes. Here, the aim is to study genome-wide regulatory effects of mRNA 5'-UTR folding free energies. We performed computations of secondary structures in 5'-UTRs and their folding free energies for all verified genes in S. cerevisiae. We found significant correlations between folding free energies of 5'-UTRs and various transcript features measured in genome-wide studies of yeast. In particular, mRNAs with weakly folded 5'-UTRs have higher translation rates, higher abundances of the corresponding proteins, longer half-lives, and higher numbers of transcripts, and are upregulated after heat shock. Furthermore, 5'-UTRs have significantly higher folding free energies than other genomic regions and randomized sequences. We also found a positive correlation between transcript half-life and ribosome occupancy that is more pronounced for short-lived transcripts, which supports a picture of competition between translation and degradation. Among the genes with strongly folded 5'-UTRs, there is a huge overrepresentation of uncharacterized open reading frames. Based on our analysis, we conclude that (i) there is a widespread bias for 5'-UTRs to be weakly folded, (ii) folding free energies of 5'-UTRs are correlated with mRNA translation and turnover on a genomic scale, and (iii) transcripts with strongly folded 5'-UTRs are often rare and hard to find experimentally.
authors.affiliation: Complex Systems Division, Department of Theoretical Physics, Lund University, Lund, Sweden. markus@thep.lu.se
authors.forename: Markus
authors.initials: M
authors.lastname: Ringnér
authors.forename: Morten
authors.initials: M
authors.lastname: Krogh
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal / Q000235:genetics*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013816:Thermodynamics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins