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dc.contributor.authorChen, Liang
dc.contributor.authorHeikkinen, Liisa
dc.contributor.authorKnott, Emily
dc.contributor.authorLiang, Yanchun
dc.contributor.authorWong, Garry
dc.date.accessioned2015-10-08T09:00:24Z
dc.date.available2015-10-08T09:00:24Z
dc.date.issued2015fi
dc.identifier.citationChen, L., Heikkinen, L., Knott, E., Liang, Y., & Wong, G. (2015). Evolutionary conservation and function of the human embryonic stem cell specific miR-302/367 cluster. <em>Comparative Biochemistry and Physiology D: Genomics and Proteomics</em>, 16, 83-98. <a href="http://dx.doi.org/10.1016/j.cbd.2015.08.002">doi:10.1016/j.cbd.2015.08.002</a>fi
dc.identifier.otherTUTKAID_67218
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/47277
dc.description.abstractmiRNA clusters define a group of related miRNAs closely localized in the genome with an evolution that remains poorly understood. The miR-302/367 cluster represents a single polycistronic transcript that produces five precursor miRNAs. The cluster is highly expressed and essential for maintenance of human embryonic stem cells. We found the cluster to be highly conserved and present in most mammals. In primates, seed sequence and miRNA structure are conserved, but inter-precursor sequences are evolving. Insertions of new miRNAs, deletions of individual miRNAs, and a cluster duplication observed in different species suggest an actively evolving cluster. Core transcriptional machinery consisting of NANOG and OCT-4 transcription factors that define stem cells are present upstream of the miR-302/367 cluster. Interestingly, we found the miR-302/367 cluster flanking region to be enriched as a target site of other miRNAs suggesting a mechanism for feedback control. Analysis of miR- 302 and miR-367 targets demonstrated concordance of gene set enrichment groups at high gene ontology levels. This cluster also expresses isomiRs providing another means of establishing sequence diversity. Finally, using three different kidney tumor datasets, we observed consistent expression of miR-302 family members in normal tissue while adjacent tumor tissue showed a significant lack of expression. Clustering expression levels of miR- 302 validated target genes showed a significant correlation between miR-302/367 cluster miRNAs and a subset of validated gene targets in healthy and adjacent tumor tissues. Taken together, our data show a highly conserved and still evolving miRNA cluster that may have additional unrecognized functions.fi
dc.language.isoeng
dc.publisherElsevier Inc.
dc.relation.ispartofseriesComparative Biochemistry and Physiology D: Genomics and Proteomics
dc.subject.otherCancerfi
dc.subject.otherFunctional genomicsfi
dc.subject.othermiRNAfi
dc.subject.otherStem cellsfi
dc.subject.otherTarget analysisfi
dc.titleEvolutionary conservation and function of the human embryonic stem cell specific miR-302/367 clusterfi
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201509293287
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosThe Department of Biological and Environmental Scienceen
dc.contributor.oppiaineEkologia ja evoluutiobiologia
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2015-09-29T15:15:03Z
dc.type.coarjournal article
dc.description.reviewstatuspeerReviewed
dc.format.pagerange83-98
dc.relation.issn1744-117X
dc.relation.volume16
dc.type.versionpublishedVersion
dc.rights.copyright© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.accesslevelopenAccessfi
dc.rights.urlhttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.relation.doi10.1016/j.cbd.2015.08.002


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© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).