ArticleBMC bioinformatics2007
Identification of putative regulatory upstream ORFs in the yeast genome using heuristics and evolutionary conservation.
Article in BMC bioinformatics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 50 citations in OpenAlex.
- Depletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expression.Molecular cell · 2024Article
- Functional Consequences of Shifting Transcript Boundaries in Glucose Starvation.Molecular and cellular biology · 2023Article
- Alternative Transcription Start Site Usage and Functional Implications in Pathogenic Fungi.Journal of fungi (Basel, Switzerland) · 2022Review
- Novel pipeline identifies new upstream ORFs and non-AUG initiating main ORFs with conserved amino acid sequences in the 5' leader of mRNAs inRNA (New York, N.Y.) · 2019Article
- A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin.Cancer & metabolism · 2019Article
- Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data.Genome research · 2018Article
- Translational control of lipogenic enzymes in the cell cycle of synchronous, growing yeast cells.The EMBO journal · 2017Article
- Upstream Open Reading Frames Differentially Regulate Gene-specific Translation in the Integrated Stress Response.The Journal of biological chemistry · 2016Review
- In-depth analysis of cis-determinants that either promote or inhibit reinitiation on GCN4 mRNA after translation of its four short uORFs.RNA (New York, N.Y.) · 2016Article
- Down-Regulating CsHT1, a Cucumber Pollen-Specific Hexose Transporter, Inhibits Pollen Germination, Tube Growth, and Seed Development.Plant physiology · 2015Article
- Fail-safe mechanism of GCN4 translational control--uORF2 promotes reinitiation by analogous mechanism to uORF1 and thus secures its key role in GCN4 expression.Nucleic acids research · 2014Article
- Emerging evidence for functional peptides encoded by short open reading frames.Nature reviews. Genetics · 2014Review
- A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.PloS one · 2014Article
- Roles for transcript leaders in translation and mRNA decay revealed by transcript leader sequencing.Genome research · 2013Article
- Extensive transcript diversity and novel upstream open reading frame regulation in yeast.G3 (Bethesda, Md.) · 2013Article
- Selective constraint on the upstream open reading frames that overlap with coding sequences in animals.PloS one · 2012Article
- Evolution of 5' untranslated region length and gene expression reprogramming in yeasts.Molecular biology and evolution · 2012Article
- Exploring the selective constraint on the sizes of insertions and deletions in 5' untranslated regions in mammals.BMC evolutionary biology · 2011Article
- Nonsense-mediated mRNA decay maintains translational fidelity by limiting magnesium uptake.Genes & development · 2010Article
- Stress-dependent coordination of transcriptome and translatome in yeast.PLoS biology · 2009Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe translational efficiency of an mRNA can be modulated by upstream open reading frames (uORFs) present in certain genes. A uORF can attenuate translation of the main ORF by interfering with translational reinitiation at the main start codon. uORFs also occur by chance in the genome, in which case they do not have a regulatory role. Since the sequence determinants for functional uORFs are not understood, it is difficult to discriminate functional from spurious uORFs by sequence analysis.
resultsWe have used comparative genomics to identify novel uORFs in yeast with a high likelihood of having a translational regulatory role. We examined uORFs, previously shown to play a role in regulation of translation in Saccharomyces cerevisiae, for evolutionary conservation within seven Saccharomyces species. Inspection of the set of conserved uORFs yielded the following three characteristics useful for discrimination of functional from spurious uORFs: a length between 4 and 6 codons, a distance from the start of the main ORF between 50 and 150 nucleotides, and finally a lack of overlap with, and clear separation from, neighbouring uORFs. These derived rules are inherently associated with uORFs with properties similar to the GCN4 locus, and may not detect most uORFs of other types. uORFs with high scores based on these rules showed a much higher evolutionary conservation than randomly selected uORFs. In a genome-wide scan in S. cerevisiae, we found 34 conserved uORFs from 32 genes that we predict to be functional; subsequent analysis showed the majority of these to be located within transcripts. A total of 252 genes were found containing conserved uORFs with properties indicative of a functional role; all but 7 are novel. Functional content analysis of this set identified an overrepresentation of genes involved in transcriptional control and development.
conclusionEvolutionary conservation of uORFs in yeasts can be traced up to 100 million years of separation. The conserved uORFs have certain characteristics with respect to length, distance from each other and from the main start codon, and folding energy of the sequence. These newly found characteristics can be used to facilitate detection of other conserved uORFs.
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