Folding free energies of 5'-UTRs impact post-transcriptional regulation on a genomic scale in yeast.
PLoS Comput Biol
; 1(7): e72, 2005 Dec.
Article
en En
| MEDLINE
| ID: mdl-16355254
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.
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Banco de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Regulación Fúngica de la Expresión Génica
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Genoma Fúngico
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Regiones no Traducidas 5'
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Proteínas de Saccharomyces cerevisiae
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Conformación de Ácido Nucleico
Tipo de estudio:
Clinical_trials
Idioma:
En
Año:
2005
Tipo del documento:
Article