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

Markus Ringnér, Morten Krogh

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)585-592
    JournalPLoS Computational Biology
    Volume1
    Issue number7
    DOIs
    Publication statusPublished - 2005 Dec 9

    Subject classification (UKÄ)

    • Bioinformatics and Systems Biology

    Fingerprint

    Dive into the research topics of 'Folding free energies of 5'-UTRs impact post-transcriptional regulation on a genomic scale in yeast'. Together they form a unique fingerprint.

    Cite this