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http://hdl.handle.net/10261/213146
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dc.contributor.author | Giráldez, María D. | - |
dc.contributor.author | Spengler, Ryan M. | - |
dc.contributor.author | Etheridge, Alton | - |
dc.contributor.author | Goicochea, Annika J. | - |
dc.contributor.author | Tuck, Missy | - |
dc.contributor.author | Won Choi, Sung | - |
dc.contributor.author | Galas, David J. | - |
dc.contributor.author | Tewari, Muneesh | - |
dc.date.accessioned | 2020-06-03T10:07:19Z | - |
dc.date.available | 2020-06-03T10:07:19Z | - |
dc.date.issued | 2019-06-03 | - |
dc.identifier | e-issn: 1460-2075 | - |
dc.identifier.citation | EMBO Journal 38(11): e101695 (2019) | - |
dc.identifier.issn | 0261-4189 | - |
dc.identifier.uri | http://hdl.handle.net/10261/213146 | - |
dc.description.abstract | Extracellular RNA s (exRNA s) in biofluids have attracted great interest as potential biomarkers. Although extracellular microRNA s in blood plasma are extensively characterized, extracellular messenger RNA (mRNA ) and long non‐coding RNA (lncRNA ) studies are limited. We report that plasma contains fragmented mRNA s and lncRNA s that are missed by standard small RNA ‐seq protocols due to lack of 5′ phosphate or presence of 3′ phosphate. These fragments were revealed using a modified protocol (“phospho‐RNA ‐seq”) incorporating RNA treatment with T4‐polynucleotide kinase, which we compared with standard small RNA ‐seq for sequencing synthetic RNA s with varied 5′ and 3′ ends, as well as human plasma exRNA . Analyzing phospho‐RNA ‐seq data using a custom, high‐stringency bioinformatic pipeline, we identified mRNA /lncRNA transcriptome fingerprints in plasma, including tissue‐specific gene sets. In a longitudinal study of hematopoietic stem cell transplant patients, bone marrow‐ and liver‐enriched exRNA genes were tracked with bone marrow recovery and liver injury, respectively, providing proof‐of‐concept validation as a biomarker approach. By enabling access to an unexplored realm of mRNA and lncRNA fragments, phospho‐RNA ‐seq opens up new possibilities for plasma transcriptomic biomarker development. | - |
dc.description.sponsorship | We acknowledge funding support from the NIH Extracellular RNA Communication Common Fund grants: U01 grants HL126499 to M. Tewari and HL126496 to D.J.G., and from the A. Alfred Taubman Medical Research Institute (Grand Challenge Award) to M. Tewari and S.W.C. Research reported in this publication was also supported by the National Cancer Institute of the NIH under Award Number P30CA046592 by the use of the following Cancer Center Shared Resource at the University of Michigan: DNA Sequencing. M.D.G. acknowledges support from a Precision Health Scholar Award from the University of Michigan Precision Health Center and a Juan Rodes contract (JR18/00026) funded by the Spanish Institute of Health Carlos III from the Ministry of Economy and Competitiveness (co‐funded by European Social Fund (ESF)). D.J.G. also acknowledges a special technology support award and partial funding from the Pacific Northwest Research Institute to his laboratory. | - |
dc.language | eng | - |
dc.publisher | EMBO Press | - |
dc.rights | closedAccess | - |
dc.title | Phospho-RNA-seq: a modified small RNA-seq method that reveals circulating mRNA and lncRNA fragments as potential biomarkers in human plasma | - |
dc.type | artículo | - |
dc.identifier.doi | 10.15252/embj.2019101695 | - |
dc.relation.publisherversion | http://dx.doi.org/10.15252/embj.2019101695 | - |
dc.date.updated | 2020-06-03T10:07:20Z | - |
dc.contributor.funder | National Institutes of Health (US) | - |
dc.contributor.funder | National Cancer Institute (US) | - |
dc.contributor.funder | University of Michigan | - |
dc.contributor.funder | Instituto de Salud Carlos III | - |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | - |
dc.contributor.funder | European Commission | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100007270 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100000002 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004587 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.pmid | 31053596 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.openairetype | artículo | - |
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