Advanced

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

Ringnér, Markus LU 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)
Please use this url to cite or link to this publication:
author
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
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
2007-08-13 14:27:29
date last changed
2017-10-22 03:45:03
@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},
  number       = {7},
  pages        = {585--592},
  publisher    = {Public Library of Science},
  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},
  volume       = {1},
  year         = {2005},
}