Folding free energies of 5'-UTRs impact post-transcriptional regulation on a genomic scale in yeast

PLoS Comput Biol. 2005 Dec;1(7):e72. doi: 10.1371/journal.pcbi.0010072. Epub 2005 Dec 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / chemistry*
  • 5' Untranslated Regions / genetics*
  • 5' Untranslated Regions / metabolism
  • Base Sequence
  • Gene Expression Regulation, Fungal*
  • Genome, Fungal / genetics*
  • Molecular Sequence Data
  • Nucleic Acid Conformation*
  • Protein Biosynthesis
  • RNA-Binding Proteins / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Thermodynamics
  • Transcription, Genetic / genetics

Substances

  • 5' Untranslated Regions
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins