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

Ringnér, Markus LU orcid and Krogh, Morten LU (2005) In PLoS Computational Biology 1(7). p.585-592
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,... (More)
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. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Computational Biology
volume
1
issue
7
pages
585 - 592
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000239480500007
  • scopus:55449088127
ISSN
1553-7358
DOI
10.1371/journal.pcbi.0010072
language
English
LU publication?
yes
id
0e60ade5-938f-4dc4-bcba-dc85722ead4b (old id 398648)
date added to LUP
2016-04-01 12:04:52
date last changed
2024-04-23 04:17:30
@article{0e60ade5-938f-4dc4-bcba-dc85722ead4b,
  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.}},
  author       = {{Ringnér, Markus and Krogh, Morten}},
  issn         = {{1553-7358}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{7}},
  pages        = {{585--592}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Computational Biology}},
  title        = {{Folding free energies of 5'-UTRs impact post-transcriptional regulation on a genomic scale in yeast}},
  url          = {{http://dx.doi.org/10.1371/journal.pcbi.0010072}},
  doi          = {{10.1371/journal.pcbi.0010072}},
  volume       = {{1}},
  year         = {{2005}},
}