{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:35:56Z","timestamp":1759962956311},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: We have recently characterized an instance of alternative splicing that differs from the canonical gene transcript by deletion of a length of sequence not divisible by three, but where translation can be rescued by an alternative start codon. This results in a predicted protein in which the amino terminus differs markedly in sequence from the known protein product(s), as it is translated from an alternative reading frame. Automated pipelines have annotated thousands of splice variants but have overlooked these protein isoforms, leading to them being underrepresented in current databases.<\/jats:p>\n               <jats:p>Results: Here we describe 1849 human and 733 mouse transcripts that can be transcribed from an alternate ATG. Of these, &amp;gt;80% have not been annotated previously. Those conserved between human and mouse genomes (and hence under likely evolutionary selection) are identified. We provide mass spectroscopy evidence for translation of selected transcripts. Of the described splice variants, only one has previously been studied in detail and converted the encoded protein from an activator of cell-function to a suppressor, demonstrating that these splice variants can result in profound functional change. We investigate the potential functional effects of this splicing using a variety of bioinformatic tools. The 2582 variants we describe are involved in a wide variety of biological processes, and therefore open many new avenues of research.<\/jats:p>\n               <jats:p>Contact: \u00a0aude.fahrer@anu.edu.au<\/jats:p>\n               <jats:p>Supplementary Inforation: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt668","type":"journal-article","created":{"date-parts":[[2013,11,22]],"date-time":"2013-11-22T01:49:40Z","timestamp":1385084980000},"page":"151-156","source":"Crossref","is-referenced-by-count":9,"title":["A novel splicing outcome reveals more than 2000 new mammalian protein isoforms"],"prefix":"10.1093","volume":"30","author":[{"given":"Laurence O. W.","family":"Wilson","sequence":"first","affiliation":[{"name":"1 Research School of Biology, Australian National University, Canberra, ACT 0200 and 2CSIRO Plant Industry, Black Mountain Laboratories, Canberra, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Spriggs","sequence":"additional","affiliation":[{"name":"1 Research School of Biology, Australian National University, Canberra, ACT 0200 and 2CSIRO Plant Industry, Black Mountain Laboratories, Canberra, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"1 Research School of Biology, Australian National University, Canberra, ACT 0200 and 2CSIRO Plant Industry, Black Mountain Laboratories, Canberra, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aude M.","family":"Fahrer","sequence":"additional","affiliation":[{"name":"1 Research School of Biology, Australian National University, Canberra, ACT 0200 and 2CSIRO Plant Industry, Black Mountain Laboratories, Canberra, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,11,20]]},"reference":[{"key":"2023012710385396100_btt668-B1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"2023012710385396100_btt668-B2","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1126\/science.1230612","article-title":"The evolutionary landscape of alternative splicing in vertebrate species","volume":"338","author":"Barbosa-Morais","year":"2012","journal-title":"Science"},{"key":"2023012710385396100_btt668-B3","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1093\/nar\/gkq806","article-title":"Alternative translation start sites are conserved in eukaryotic genomes","volume":"39","author":"Bazykin","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2023012710385396100_btt668-B4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1089\/cmb.2008.0028","article-title":"Detecting alternative gene structures from spliced ESTs: a computational approach","volume":"16","author":"Bonizzoni","year":"2009","journal-title":"J. Comput. Biol."},{"key":"2023012710385396100_btt668-B5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0014-5793(00)01581-7","article-title":"EST comparison indicates 38% of human mRNAs contain possible alternative splice forms","volume":"474","author":"Brett","year":"2000","journal-title":"FEBS Lett."},{"key":"2023012710385396100_btt668-B6","doi-asserted-by":"crossref","first-page":"10505","DOI":"10.1128\/MCB.24.24.10505-10514.2004","article-title":"Influence of RNA secondary structure on the pre-mRNA splicing process","volume":"24","author":"Buratti","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"2023012710385396100_btt668-B7","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1371\/journal.pcbi.0030091","article-title":"A first look at ARFome: dual-coding genes in mammalian genomes","volume":"3","author":"Chung","year":"2007","journal-title":"PLoS Comput. Biol."},{"key":"2023012710385396100_btt668-B8","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1242\/jcs.044610","article-title":"The conserved metalloprotease invadolysin localizes to the surface of lipid droplets","volume":"122","author":"Cobbe","year":"2009","journal-title":"J. Cell Sci."},{"key":"2023012710385396100_btt668-B9","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1093\/bioinformatics\/bth092","article-title":"TANDEM: matching proteins with tandem mass spectra","volume":"20","author":"Craig","year":"2004","journal-title":"Bioinformatics"},{"key":"2023012710385396100_btt668-B35","first-page":"1090","article-title":"Using RNAFOLD to predict the activity of small catalytic RNAs","volume":"15","author":"Denman","year":"1993","journal-title":"Biotechniques"},{"key":"2023012710385396100_btt668-B10","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1186\/gb-2004-6-1-r9","article-title":"Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry","volume":"6","author":"Desiere","year":"2005","journal-title":"Genome Biol."},{"key":"2023012710385396100_btt668-B11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nmeth1019","article-title":"Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry","volume":"4","author":"Elias","year":"2007","journal-title":"Nat. Methods"},{"key":"2023012710385396100_btt668-B12","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1101\/gr.1862204","article-title":"ESTGenes: alternative splicing from ESTs in Ensembl","volume":"14","author":"Eyras","year":"2004","journal-title":"Genome Res."},{"key":"2023012710385396100_btt668-B13","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.gene.2006.02.022","article-title":"Characterization of the murine Inpp4b gene and identification of a novel isoform","volume":"376","author":"Ferron","year":"2006","journal-title":"Gene"},{"key":"2023012710385396100_btt668-B14","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1365-2567.2008.02831.x","article-title":"Defective T-cell function leading to reduced antibody production in a kleisin-beta mutant mouse","volume":"125","author":"Gosling","year":"2008","journal-title":"Immunology"},{"key":"2023012710385396100_btt668-B15","doi-asserted-by":"crossref","first-page":"12445","DOI":"10.1073\/pnas.0704870104","article-title":"A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development","volume":"104","author":"Gosling","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012710385396100_btt668-B16","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/ng1469","article-title":"Widespread occurrence of alternative splicing at NAGNAG acceptors contributes to proteome plasticity","volume":"36","author":"Hiller","year":"2004","journal-title":"Nat. Genet."},{"key":"2023012710385396100_btt668-B17","doi-asserted-by":"crossref","first-page":"W585","DOI":"10.1093\/nar\/gkm259","article-title":"WoLF PSORT: protein localization predictor","volume":"35","author":"Horton","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2023012710385396100_btt668-B18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang da","year":"2009","journal-title":"Nat. Protoc."},{"key":"2023012710385396100_btt668-B19","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1126\/science.1168978","article-title":"Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling","volume":"324","author":"Ingolia","year":"2009","journal-title":"Science"},{"key":"2023012710385396100_btt668-B20","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1101\/gr.764102","article-title":"Selecting for functional alternative splices in ESTs","volume":"12","author":"Kan","year":"2002","journal-title":"Genome Res."},{"key":"2023012710385396100_btt668-B21","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1021\/ac025747h","article-title":"Empirical statistical model to estimate the accuracy of peptide identifications made by MS\/MS and database search","volume":"74","author":"Keller","year":"2002","journal-title":"Anal. Chem."},{"key":"2023012710385396100_btt668-B22","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1002\/bies.20771","article-title":"Alternative translation start sites and hidden coding potential of eukaryotic mRNAs","volume":"30","author":"Kochetov","year":"2008","journal-title":"Bioessays"},{"key":"2023012710385396100_btt668-B23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0092-8674(86)90762-2","article-title":"Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes","volume":"44","author":"Kozak","year":"1986","journal-title":"Cell"},{"key":"2023012710385396100_btt668-B24","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1093\/emboj\/16.9.2482","article-title":"Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6","volume":"16","author":"Kozak","year":"1997","journal-title":"EMBO J."},{"key":"2023012710385396100_btt668-B25","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012710385396100_btt668-B26","doi-asserted-by":"crossref","first-page":"E2424","DOI":"10.1073\/pnas.1207846109","article-title":"Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution","volume":"109","author":"Lee","year":"2012","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012710385396100_btt668-B27","doi-asserted-by":"crossref","first-page":"i275","DOI":"10.1093\/bioinformatics\/btr209","article-title":"PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions","volume":"27","author":"Lin","year":"2011","journal-title":"Bioinformatics"},{"key":"2023012710385396100_btt668-B28","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1126\/science.1228186","article-title":"Evolutionary dynamics of gene and isoform regulation in Mammalian tissues","volume":"338","author":"Merkin","year":"2012","journal-title":"Science"},{"key":"2023012710385396100_btt668-B29","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature08909","article-title":"Expansion of the eukaryotic proteome by alternative splicing","volume":"463","author":"Nilsen","year":"2010","journal-title":"Nature"},{"key":"2023012710385396100_btt668-B36","doi-asserted-by":"crossref","first-page":"D290","DOI":"10.1093\/nar\/gkr1065","article-title":"The Pfam protein families database","volume":"40","author":"Punta","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023012710385396100_btt668-B30","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1074\/mcp.M900317-MCP200","article-title":"Protein identification false discovery rates for very large proteomics data sets generated by tandem mass spectrometry","volume":"8","author":"Reiter","year":"2009","journal-title":"Mol. Cell Proteomics"},{"key":"2023012710385396100_btt668-B31","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/ni1017","article-title":"Two isoforms of otubain 1 regulate T cell anergy via GRAIL","volume":"5","author":"Soares","year":"2004","journal-title":"Nat. Immunol."},{"key":"2023012710385396100_btt668-B32","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1111\/j.1742-4658.2012.08530.x","article-title":"Splice variants of the condensin II gene Ncaph2 include alternative reading frame translations of exon 1","volume":"279","author":"Theodoratos","year":"2012","journal-title":"FEBS J."},{"key":"2023012710385396100_btt668-B33","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1080\/07391102.2010.10508575","article-title":"Interrelations between the nucleotide context of human start AUG codon, N-end amino acids of the encoded protein and initiation of translation","volume":"27","author":"Volkova","year":"2010","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2023012710385396100_btt668-B34","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/cr.2010.25","article-title":"Length of the ORF, position of the first AUG and the Kozak motif are important factors in potential dual-coding transcripts","volume":"20","author":"Xu","year":"2010","journal-title":"Cell Res."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/2\/151\/48914280\/bioinformatics_30_2_151.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/2\/151\/48914280\/bioinformatics_30_2_151.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T10:43:51Z","timestamp":1674816231000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/30\/2\/151\/226683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,20]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,1,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btt668","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,1,15]]},"published":{"date-parts":[[2013,11,20]]}}}