This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kastenmayer, J. P. Articles by Basrai, M. A. Search for Related Content PubMed PubMed Citation Articles by Kastenmayer, J. P. Articles by Basrai, M. A. Social Bookmarking                   What's this?

Letter

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

¹ Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20889, USA ² Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA ³ Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA ⁴ National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA ⁵ Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

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 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.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.4355406.

⁶ These authors contributed equally to this work.

⁷ Corresponding author.
E-mail basraim{at}nih.gov; fax (301) 480-0380.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Pierrel, O. Khalimonchuk, P. A. Cobine, M. Bestwick, and D. R. Winge Coa2 Is an Assembly Factor for Yeast Cytochrome c Oxidase Biogenesis That Facilitates the Maturation of Cox1 Mol. Cell. Biol., August 15, 2008; 28(16): 4927 - 4939. [Abstract] [Full Text] [PDF]

				W.-C. Au, M. J. Crisp, S. Z. DeLuca, O. J. Rando, and M. A. Basrai Altered Dosage and Mislocalization of Histone H3 and Cse4p Lead to Chromosome Loss in Saccharomyces cerevisiae Genetics, May 1, 2008; 179(1): 263 - 275. [Abstract] [Full Text] [PDF]

				K. Hanada, X. Zhang, J. O. Borevitz, W.-H. Li, and S.-H. Shiu A large number of novel coding small open reading frames in the intergenic regions of the Arabidopsis thaliana genome are transcribed and/or under purifying selection Genome Res., May 1, 2007; 17(5): 632 - 640. [Abstract] [Full Text] [PDF]

				L. Pena-Castillo and T. R. Hughes Why Are There Still Over 1000 Uncharacterized Yeast Genes? Genetics, May 1, 2007; 176(1): 7 - 14. [Abstract] [Full Text] [PDF]

				E. Coic, K. Sun, C. Wu, and J. E. Haber Cell Cycle-Dependent Regulation of Saccharomyces cerevisiae Donor Preference during Mating-Type Switching by SBF (Swi4/Swi6) and Fkh1. Mol. Cell. Biol., July 1, 2006; 26(14): 5470 - 5480. [Abstract] [Full Text] [PDF]