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Article: Exploring genetic associations with ceRNA regulation in the human genome

TitleExploring genetic associations with ceRNA regulation in the human genome
Authors
Issue Date2017
Citation
Nucleic Acids Research, 2017, v. 45, n. 10, p. 5653-5665 How to Cite?
AbstractCompeting endogenous RNAs (ceRNAs) are RNA molecules that sequester shared microRNAs (miRNAs) thereby affecting the expression of other targets of the miRNAs. Whether genetic variants in ceRNA can affect its biological function and disease development is still an open question. Here we identified a large number of genetic variants that are associated with ceRNA's function using Geuvaids RNA-seq data for 462 individuals from the 1000 Genomes Project. We call these loci competing endogenous RNA expression quantitative trait loci or 'cerQTL', and found that a large number of them were unexplored in conventional eQTL mapping. We identified many cerQTLs that have undergone recent positive selection in different human populations, and showed that single nucleotide polymorphisms in gene 3'UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We also discovered that cerQTLs are significantly enriched in traits/diseases associated variants reported from genome-wide association studies in the miRNA binding sites, suggesting that disease susceptibilities could be attributed to ceRNA regulation. Further in vitro functional experiments demonstrated that a cerQTL rs11540855 can regulate ceRNA function. These results provide a comprehensive catalog of functional non-coding regulatory variants that may be responsible for ceRNA crosstalk at the post-transcriptional level.
Persistent Identifierhttp://hdl.handle.net/10722/324493
ISSN
2023 Impact Factor: 16.6
2023 SCImago Journal Rankings: 7.048
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Mulin Jun-
dc.contributor.authorZhang, Jian-
dc.contributor.authorLiang, Qian-
dc.contributor.authorXuan, Chenghao-
dc.contributor.authorWu, Jiexing-
dc.contributor.authorJiang, Peng-
dc.contributor.authorLi, Wei-
dc.contributor.authorZhu, Yun-
dc.contributor.authorWang, Panwen-
dc.contributor.authorFernandez, Daniel-
dc.contributor.authorShen, Yujun-
dc.contributor.authorChen, Yiwen-
dc.contributor.authorKocher, Jean Pierre A.-
dc.contributor.authorYu, Ying-
dc.contributor.authorSham, Pak Chung-
dc.contributor.authorWang, Junwen-
dc.contributor.authorLiu, Jun S.-
dc.contributor.authorLiu, X. Shirley-
dc.date.accessioned2023-02-03T07:03:26Z-
dc.date.available2023-02-03T07:03:26Z-
dc.date.issued2017-
dc.identifier.citationNucleic Acids Research, 2017, v. 45, n. 10, p. 5653-5665-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/324493-
dc.description.abstractCompeting endogenous RNAs (ceRNAs) are RNA molecules that sequester shared microRNAs (miRNAs) thereby affecting the expression of other targets of the miRNAs. Whether genetic variants in ceRNA can affect its biological function and disease development is still an open question. Here we identified a large number of genetic variants that are associated with ceRNA's function using Geuvaids RNA-seq data for 462 individuals from the 1000 Genomes Project. We call these loci competing endogenous RNA expression quantitative trait loci or 'cerQTL', and found that a large number of them were unexplored in conventional eQTL mapping. We identified many cerQTLs that have undergone recent positive selection in different human populations, and showed that single nucleotide polymorphisms in gene 3'UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We also discovered that cerQTLs are significantly enriched in traits/diseases associated variants reported from genome-wide association studies in the miRNA binding sites, suggesting that disease susceptibilities could be attributed to ceRNA regulation. Further in vitro functional experiments demonstrated that a cerQTL rs11540855 can regulate ceRNA function. These results provide a comprehensive catalog of functional non-coding regulatory variants that may be responsible for ceRNA crosstalk at the post-transcriptional level.-
dc.languageeng-
dc.relation.ispartofNucleic Acids Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleExploring genetic associations with ceRNA regulation in the human genome-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/nar/gkx331-
dc.identifier.pmid28472449-
dc.identifier.pmcidPMC5449616-
dc.identifier.scopuseid_2-s2.0-85021949548-
dc.identifier.volume45-
dc.identifier.issue10-
dc.identifier.spage5653-
dc.identifier.epage5665-
dc.identifier.eissn1362-4962-
dc.identifier.isiWOS:000402510700020-

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