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.
Highlights
Regulation of gene expression is important for many cellular processes
We found that 59-untranslated region (UTR) on average are more weakly folded than random sequences with the same dinucleotide frequencies, and than intergenic, coding, and 39-UTR sequences
Folding Free Energies of 59-UTRs and Transcript Features We investigated the correlation between DG and the ribosome density measured by Arava et al [30]
Summary
Numerous studies have focused on the transcriptional level to investigate under what conditions a gene is transcribed and to what extent These investigations have led to descriptions of system architectures, in which the activity of specific transcription factors regulates the activity of downstream target genes in such a way that the combined activity results in large developmental or physiological programs. In recent years, such descriptions have benefited from DNA microarray technology, which has provided overall mRNA levels for many systems. Ribosomal scanning is severely hampered by 59-UTRs containing start codons or secondary structure [9,10,11,12,13,14,15]
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