Functional genomics of genes with small open reading frames ( sORFs ) in S. Cerevisiae

Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20889, USA.
Genome Research (Impact Factor: 14.63). 04/2006; 16(3):365-73. DOI: 10.1101/gr.4355406
Source: PubMed


Genes with small open reading frames (sORFs; <100 amino acids) represent an untapped source of important biology. sORFs largely escaped analysis because they were difficult to predict computationally and less likely to be targeted by genetic screens. Thus, the substantial number of sORFs and their potential importance have only recently become clear. To investigate sORF function, we undertook the first functional studies of sORFs in any system, using the model eukaryote Saccharomyces cerevisiae. Based on independent experimental approaches and computational analyses, evidence exists for 299 sORFs in the S. cerevisiae genome, representing approximately 5% of the annotated ORFs. We determined that a similar percentage of sORFs are annotated in other eukaryotes, including humans, and 184 of the S. cerevisiae sORFs exhibit similarity with ORFs in other organisms. To investigate sORF function, we constructed a collection of gene-deletion mutants of 140 newly identified sORFs, each of which contains a strain-specific "molecular barcode," bringing the total number of sORF deletion strains to 247. Phenotypic analyses of the new gene-deletion strains identified 22 sORFs required for haploid growth, growth at high temperature, growth in the presence of a nonfermentable carbon source, or growth in the presence of DNA damage and replication-arrest agents. We provide a collection of sORF deletion strains that can be integrated into the existing deletion collection as a resource for the yeast community for elucidating gene function. Moreover, our analyses of the S. cerevisiae sORFs establish that sORFs are conserved across eukaryotes and have important biological functions.

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Available from: Ronald Davis, Oct 12, 2014
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    • "The LSO1 gene (YJR005C-A) was not found in the initial study (Shakoury-Elizeh et al. 2004) and is the most increased by BPS with an over 200-fold increase in the mRNA (Table 2). LSO1 was not known during that original study because it was " late-annotated small open reading frame " as the LSO1 encodes a small 93 amino acid gene product not annotated in the original yeast genome project (Goffeau et al. 1996; Cliften et al. 2003; Kastenmayer et al. 2006). LSO1 was annotated after being found by homology with the genome of the filamentous fungus Ashbya gossypii (Brachat et al. 2003). "
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    ABSTRACT: We have identified a new downstream target gene of the Aft1/2-regulated iron regulon in budding yeast Saccharomyces cerevisiae, the late-annotated small open reading frame LSO1. LSO1 transcript is among the most highly induced from a transcriptome analysis of a fet3-1 mutant grown in the presence of the iron chelator bathophenanthrolinedisulfonic acid. LSO1 has a paralog, LSO2, which is constitutively expressed and not affected by iron availability. In contrast, we find that the LSO1 promoter region contains three consensus binding sites for the Aft1/2 transcription factors and that an LSO1-lacZ reporter is highly induced under low-iron conditions in a Aft1-dependent manner. The expression patterns of the Lso1 and Lso2 proteins mirror those of their mRNAs. Both proteins are localized to the nucleus and cytoplasm, but become more cytoplasmic upon iron deprivation consistent with a role in iron transport. LSO1 and LSO2 appear to play overlapping roles in the cellular response to iron starvation since single lso1 and lso2 mutants are sensitive to iron deprivation and this sensitivity is exacerbated when both genes are deleted.
    MicrobiologyOpen 10/2015; DOI:10.1002/mbo3.303 · 2.21 Impact Factor
    • "In another computational study, a total of 180,879 SPs were found from 491 strains of bacteria and 41 strains of archaea which means an average of ~11% proteins of a bacterial and archaeal proteome consists of SPs (Wang et al., 2008). In Saccharomyces cerevisiae 299 SPs were found out of which 22 regulates growth (Kastenmayer et al., 2006). In Hydra the number of SPs involve in biological functions are close to 800 (Bosch and Fujisawa, 2001). "
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    DESCRIPTION: The review article is about small ORFs and small proteins present in the genome and proteome, respectively, of various living systems.
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    • "As previously mentioned, several smORFs have been identified based on conservation and gene expression in fungi (Kastenmayer et al., 2006; Kessler et al., 2003). In plants, a few smORFs were identified by genetic screenings such as POLARIS, ROTUNDIFOLIA4, and Enod40. "
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    ABSTRACT: Genes containing small open reading frames (smORFs) constitute a new group of eukaryotic genes expected to represent 5% of Drosophila melanogaster transcribed genes. In this review we provide a historical perspective in their recent discovery, describe their general mechanism and discuss the importance of smORFs for future genomic and transcriptomic studies. Finally, we discuss the biological role of the mostly studied smORF studied so far, the Mlpt/Pri/Tal gene in arthropods. The pleiotropic action of Mlpt/Pri/Tal in D. melanogaster suggests a complex evolutionary scenario, which might be used to understand smORF origin, evolution and integration into complex gene regulatory networks.
    Genetics and Molecular Biology 05/2015; · 1.20 Impact Factor
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