{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:19:39Z","timestamp":1791411579123,"version":"4.3.3"},"reference-count":63,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:00:00Z","timestamp":1471305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:00:00Z","timestamp":1471305600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:00:00Z","timestamp":1471305600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK30425"],"award-info":[{"award-number":["DK30425"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK092942"],"award-info":[{"award-number":["DK092942"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Ribosomal RNA transcription mediated by RNA polymerase I represents the rate-limiting step in ribosome biogenesis. In eukaryotic cells, nutrients and growth factors regulate ribosomal RNA transcription through various key factors coupled to cell growth. We show here in mature adipocytes, ribosomal transcription can be acutely regulated in response to metabolic challenges. This acute response is mediated by PTRF (polymerase I transcription and release factor, also known as cavin-1), which has previously been shown to play a critical role in caveolae formation. The caveolae\u2013independent rDNA transcriptional role of PTRF not only explains the lipodystrophy phenotype observed in PTRF deficient mice and humans, but also highlights its crucial physiological role in maintaining adipocyte allostasis. Multiple post-translational modifications of PTRF provide mechanistic bases for its regulation. The role of PTRF in ribosomal transcriptional efficiency is likely relevant to many additional physiological situations of cell growth and organismal metabolism.<\/jats:p>","DOI":"10.7554\/elife.17508","type":"journal-article","created":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T19:59:09Z","timestamp":1471291149000},"source":"Crossref","is-referenced-by-count":61,"title":["PTRF\/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges"],"prefix":"10.7554","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5056-1517","authenticated-orcid":true,"given":"Libin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Boston University School of Medicine, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1997-0499","authenticated-orcid":true,"given":"Paul F","family":"Pilch","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Boston University School of Medicine, Boston, United States"},{"name":"Department of Medicine, Boston University School of Medicine, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2016,8,16]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.2337\/db10-0744","article-title":"Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism","volume":"60","author":"Aboulaich","year":"2011","journal-title":"Diabetes"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.bbrc.2006.09.094","article-title":"Association and insulin regulated translocation of hormone-sensitive lipase with PTRF","volume":"350","author":"Aboulaich","year":"2006","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1042\/BJ20040647","article-title":"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes","volume":"383","author":"Aboulaich","year":"2004","journal-title":"Biochemical Journal"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-14-89","article-title":"Novel PTRF mutation in a child with mild myopathy and very mild congenital lipodystrophy","volume":"14","author":"Ardissone","year":"2013","journal-title":"BMC Medical Genetics"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1083\/jcb.200903053","article-title":"MURC\/Cavin-4 and cavin family members form tissue-specific caveolar complexes","volume":"185","author":"Bastiani","year":"2009","journal-title":"\u00a0Journal of Cell Biology"},{"key":"bib6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0022-2275(20)39294-4","article-title":"RNA biosynthesis in adipose tissue: effect of fasting","volume":"7","author":"Benjamin","year":"1966","journal-title":"Journal of Lipid Research"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.cmet.2013.06.019","article-title":"Metabolic regulation by p53 family members","volume":"18","author":"Berkers","year":"2013","journal-title":"Cell Metabolism"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"4207","DOI":"10.1128\/MCB.16.8.4207","article-title":"Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay","volume":"16","author":"Bogerd","year":"1996","journal-title":"Molecular and Cellular Biology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nrc3496","article-title":"Dysregulation of the basal RNA polymerase transcription apparatus in cancer","volume":"13","author":"Bywater","year":"2013","journal-title":"Nature Reviews Cancer"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/ncb1562","article-title":"C-terminal modifications regulate MDM2 dissociation and nuclear export of p53","volume":"9","author":"Carter","year":"2007","journal-title":"Nature Cell Biology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"3062","DOI":"10.1128\/MCB.01824-08","article-title":"Masking of a nuclear signal motif by monoubiquitination leads to mislocalization and degradation of the regulatory enzyme cytidylyltransferase","volume":"29","author":"Chen","year":"2009","journal-title":"Molecular and Cellular Biology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1073\/pnas.84.3.629","article-title":"Nucleotide sequence determining the first cleavage site in the processing of mouse precursor rRNA","volume":"84","author":"Craig","year":"1987","journal-title":"PNAS"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/embor.2011.8","article-title":"A model for the topology of active ribosomal RNA genes","volume":"12","author":"Denissov","year":"2011","journal-title":"EMBO Reports"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"8473","DOI":"10.1074\/jbc.M113.546242","article-title":"Pleiotropic effects of cavin-1 deficiency on lipid metabolism","volume":"289","author":"Ding","year":"2014","journal-title":"Journal of Biological Chemistry"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.ymgme.2010.06.016","article-title":"A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4","volume":"101","author":"Dwianingsih","year":"2010","journal-title":"Molecular Genetics and Metabolism"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.molcel.2006.04.002","article-title":"Reversible monoubiquitination of PCNA: A novel slant on regulating translesion DNA synthesis","volume":"22","author":"Friedberg","year":"2006","journal-title":"Molecular Cell"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.bbagrm.2012.10.004","article-title":"Epigenetic control of RNA polymerase I transcription in mammalian cells","volume":"1829","author":"Grummt","year":"2013","journal-title":"Biochimica et Biophysica Acta"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1101\/gad.1098503R","article-title":"Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus","volume":"17","author":"Grummt","year":"2003","journal-title":"Genes & Development"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"4626","DOI":"10.1111\/j.1742-4658.2010.07892.x","article-title":"Wisely chosen paths--regulation of rRNA synthesis: delivered on 30 June 2010 at the 35th FEBS Congress in Gothenburg, Sweden","volume":"277","author":"Grummt","year":"2010","journal-title":"The FEBS Journal"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"14112","DOI":"10.1073\/pnas.0806158105","article-title":"Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS","volume":"105","author":"Guha","year":"2008","journal-title":"PNAS"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"4905","DOI":"10.1093\/nar\/13.13.4905","article-title":"Characterization of mouse 45S ribosomal RNA subspecies suggests that the first processing cleavage occurs 600 +\/- 100 nucleotides from the 5' end and the second 500 +\/- 100 nucleotides from the 3' end of a 13.9 kb precursor","volume":"13","author":"Gurney","year":"1985","journal-title":"Nucleic Acids Research"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1432-1033.1985.tb09073.x","article-title":"Insulin-stimulated protein synthesis in adipocytes. Enhanced rate of initiation associated with increased phosphorylation of ribosomal protein S6","volume":"151","author":"Hansson","year":"1985","journal-title":"European Journal of Biochemistry"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1172\/JCI38660","article-title":"Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy","volume":"119","author":"Hayashi","year":"2009","journal-title":"Journal of Clinical Investigation"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.1073\/pnas.69.11.3394","article-title":"Location of ribosomal DNA in the human chromosome complement","volume":"69","author":"Henderson","year":"1972","journal-title":"PNAS"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.cell.2007.11.042","article-title":"PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function","volume":"132","author":"Hill","year":"2008","journal-title":"Cell"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.cmet.2013.04.010","article-title":"Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2","volume":"17","author":"Humphrey","year":"2013","journal-title":"Cell Metabolism"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1093\/nar\/29.2.423","article-title":"The transcript release factor PTRF augments ribosomal gene transcription by facilitating reinitiation of RNA polymerase I","volume":"29","author":"Jansa","year":"2001","journal-title":"Nucleic Acids Research"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1007\/s004380051112","article-title":"Mechanism of transcription termination: PTRF interacts with the largest subunit of RNA polymerase I and dissociates paused transcription complexes from yeast and mouse","volume":"262","author":"Jansa","year":"1999","journal-title":"Molecular and General Genetics MGG"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"2855","DOI":"10.1093\/emboj\/17.10.2855","article-title":"Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes","volume":"17","author":"Jansa","year":"1998","journal-title":"The EMBO Journal"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.ejmg.2015.02.002","article-title":"Novel nonsense mutation in the PTRF gene underlies congenital generalized lipodystrophy in a consanguineous Saudi family","volume":"58","author":"Jelani","year":"2015","journal-title":"European Journal of Medical Genetics"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/0092-8674(84)90457-4","article-title":"A short amino acid sequence able to specify nuclear location","volume":"39","author":"Kalderon","year":"1984","journal-title":"Cell"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"e11015","DOI":"10.1371\/journal.pone.0011015","article-title":"The early nutritional environment of mice determines the capacity for adipose tissue expansion by modulating genes of caveolae structure","volume":"5","author":"Kozak","year":"2010","journal-title":"PLoS One"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.gene.2014.11.010","article-title":"Regulation of rDNA transcription in response to growth factors, nutrients and energy","volume":"556","author":"Kusnadi","year":"2015","journal-title":"Gene"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"5735","DOI":"10.1038\/sj.emboj.7601454","article-title":"NoRC-dependent nucleosome positioning silences rRNA genes","volume":"25","author":"Li","year":"2006","journal-title":"The EMBO Journal"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.cmet.2008.07.008","article-title":"Deletion of Cavin\/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance","volume":"8","author":"Liu","year":"2008","journal-title":"Cell Metabolism"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"4249","DOI":"10.1091\/mbc.E06-04-0278","article-title":"Role of insulin-dependent cortical fodrin\/spectrin remodeling in glucose transporter 4 translocation in rat adipocytes","volume":"17","author":"Liu","year":"2006","journal-title":"Molecular Biology of the Cell"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"4314","DOI":"10.1074\/jbc.M707890200","article-title":"A critical role of cavin (polymerase I and transcript release factor) in caveolae formation and organization","volume":"283","author":"Liu","year":"2008","journal-title":"Journal of Biological Chemistry"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/0092-8674(81)90370-6","article-title":"Transcription of mouse rRNA genes by RNA polymerase I: in vitro and in vivo initiation and processing sites","volume":"27","author":"Miller","year":"1981","journal-title":"Cell"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00018-006-6278-1","article-title":"A housekeeper with power of attorney: the rRNA genes in ribosome biogenesis","volume":"64","author":"Moss","year":"2007","journal-title":"Cellular and Molecular Life Sciences"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/emboj.2008.57","article-title":"Epigenetic regulation of TTF-I-mediated promoter-terminator interactions of rRNA genes","volume":"27","author":"N\u00e9meth","year":"2008","journal-title":"The EMBO Journal"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.tig.2011.01.002","article-title":"Genome organization in and around the nucleolus","volume":"27","author":"N\u00e9meth","year":"2011","journal-title":"Trends in Genetics"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/nrm3512","article-title":"Caveolae as plasma membrane sensors, protectors and organizers","volume":"14","author":"Parton","year":"2013","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1600-0854.2005.00270.x","article-title":"Mechanisms of receptor-mediated nuclear import and nuclear export","volume":"6","author":"Pemberton","year":"2005","journal-title":"Traffic"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.tem.2011.04.001","article-title":"Fat caves: caveolae, lipid trafficking and lipid metabolism in adipocytes","volume":"22","author":"Pilch","year":"2011","journal-title":"Trends in Endocrinology & Metabolism"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1194\/jlr.R700009-JLR200","article-title":"Cellular spelunking: exploring adipocyte caveolae","volume":"48","author":"Pilch","year":"2007","journal-title":"Journal of Lipid Research"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/BF02510486","article-title":"Early stages of pre-rRNA formation within the nucleolar ultrastructure of mouse cells studied by in situ hybridization with a 5'ETS leader probe","volume":"105","author":"Puvion-Dutilleul","year":"1997","journal-title":"Chromosoma"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cell.2013.12.012","article-title":"What we talk about when we talk about fat","volume":"156","author":"Rosen","year":"2014","journal-title":"Cell"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.tibs.2004.12.008","article-title":"RNA-polymerase-I-directed rDNA transcription, life and works","volume":"30","author":"Russell","year":"2005","journal-title":"Trends in Biochemical Sciences"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1093\/nar\/25.6.1142","article-title":"Oligomerization of the transcription termination factor TTF-I: implications for the structural organization of ribosomal transcription units","volume":"25","author":"Sander","year":"1997","journal-title":"Nucleic Acids Research"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.2337\/db06-0263","article-title":"Adipose tissue","volume":"55","author":"Scherer","year":"2006","journal-title":"From lipid storage compartment to endocrine organ. Diabetes"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.gene.2011.08.006","article-title":"RNA polymerase I activity is regulated at multiple steps in the transcription cycle: recent insights into factors that influence transcription elongation","volume":"493","author":"Schneider","year":"2012","journal-title":"Gene"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1002\/ajmg.a.33578","article-title":"Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations","volume":"152A","author":"Shastry","year":"2010","journal-title":"American Journal of Medical Genetics Part A"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1038\/onc.2009.21","article-title":"c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells","volume":"28","author":"Shiue","year":"2009","journal-title":"Oncogene"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"18321","DOI":"10.1074\/jbc.M211541200","article-title":"Immunopurification and characterization of rat adipocyte caveolae suggest their dissociation from insulin signaling","volume":"278","author":"Souto","year":"2003","journal-title":"Journal of Biological Chemistry"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1101\/gr.6858507","article-title":"Genomic architecture and inheritance of human ribosomal RNA gene clusters","volume":"18","author":"Stults","year":"2008","journal-title":"Genome Research"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1172\/JCI45887","article-title":"Adipose tissue remodeling and obesity","volume":"121","author":"Sun","year":"2011","journal-title":"Journal of Clinical Investigation"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s004410100389","article-title":"A 60-kDa protein abundant in adipocyte caveolae","volume":"305","author":"Vinten","year":"2001","journal-title":"Cell and Tissue Research"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.cell.2009.04.037","article-title":"Blinded by the light: The growing complexity of p53","volume":"137","author":"Vousden","year":"2009","journal-title":"Cell"},{"key":"bib59","first-page":"E121","article-title":"Insulin regulation of fat cell ribosomes, protein synthesis, and lipoprotein lipase","volume":"245","author":"Vydelingum","year":"1983","journal-title":"The American Journal of Physiology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.bbrc.2014.12.035","article-title":"The N-terminal leucine-zipper motif in PTRF\/cavin-1 is essential and sufficient for its caveolae-association","volume":"456","author":"Wei","year":"2015","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/0006-291X(75)90506-9","article-title":"Effect of chloroquine on cultured fibroblasts: release of lysosomal hydrolases and inhibition of their uptake","volume":"66","author":"Wiesmann","year":"1975","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.bbagrm.2014.10.007","article-title":"The nucleolus as a fundamental regulator of the p53 response and a new target for cancer therapy","volume":"1849","author":"Woods","year":"2015","journal-title":"Biochimica et Biophysica Acta"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.ccr.2009.09.024","article-title":"Signaling to p53: ribosomal proteins find their way","volume":"16","author":"Zhang","year":"2009","journal-title":"Cancer Cell"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/17508\/elife-17508-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/17508\/elife-17508-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/17508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:54:15Z","timestamp":1697057655000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/17508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,16]]},"references-count":63,"alternative-id":["10.7554\/eLife.17508"],"URL":"https:\/\/doi.org\/10.7554\/elife.17508","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.17508.015","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.17508.016","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,16]]},"article-number":"e17508"}}