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Here we present an approach, global translation initiation sequencing, applying in parallel the ribosome E-site translation inhibitors lactimidomycin and cycloheximide to achieve simultaneous detection of both initiation and elongation events on a genome-wide scale. This approach provides a view of alternative translation initiation in mammalian cells with single-nucleotide resolution. Systemic analysis of TIS positions supports the ribosome linear-scanning mechanism in TIS selection. The alternative TIS positions and the associated ORFs identified by global translation initiation sequencing are conserved between human and mouse cells, implying physiological significance of alternative translation. Our study establishes a practical platform for uncovering the hidden coding potential of the transcriptome and offers a greater understanding of the complexity of translation initiation.<\/jats:p>","DOI":"10.1073\/pnas.1207846109","type":"journal-article","created":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T23:18:09Z","timestamp":1346109489000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":592,"title":["Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution"],"prefix":"10.1073","volume":"109","author":[{"given":"Sooncheol","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Nutritional Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Botao","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Field of Genetics, Genomics and Development, Cornell University, Ithaca, NY 14853;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soohyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Proboco Informatics, Ithaca, NY 14850;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Xiong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and"},{"name":"Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Bing","family":"Qian","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences and"},{"name":"Graduate Field of Genetics, Genomics and Development, Cornell University, Ithaca, NY 14853;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,27]]},"reference":[{"key":"e_1_1_2_18_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)01056-9"},{"key":"e_1_1_2_18_11_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.23.8635-8642.2000"},{"key":"e_1_1_2_18_11_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168978"},{"key":"e_1_1_2_18_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.002"},{"key":"e_1_1_2_18_11_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.304"},{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.cell.2009.01.042","article-title":"Regulation of translation initiation in eukaryotes: Mechanisms and biological targets","volume":"136","author":"Sonenberg N","year":"2009","unstructured":"N Sonenberg, AG Hinnebusch, Regulation of translation initiation in eukaryotes: Mechanisms and biological targets. 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