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Article: MicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation

TitleMicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation
Authors
Issue Date2010
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal Of Immunology, 2010, v. 184 n. 11, p. 6053-6059 How to Cite?
AbstractMicroRNAs (miRNAs) are generally recognized as regulating gene expression posttranscriptionally by inhibiting translation or inducing target mRNA degradation. New mechanisms for miRNAs to regulate gene expression also still attract much attention. More and more novel miRNAs are discovered by the advanced sequencing technology, but yet their biological functions are largely unknown. Up to now, the function of miR-466l, a miRNA discovered in mouse embryonic stem cells, remains unclear. In this study, we report that miR-466l can upregulate both mRNA and protein expression of IL-10 in TLR-triggered macrophages. Furthermore, we show that miR-466l can competitively bind to the IL-10 3′ untranslated region AU-rich elements, which is a typical binding site for RNA-binding protein (RBP). Tristetraprolin is a well-known RBP, and mediates rapid degradation of IL-10 mRNA. miRNA always mediates target mRNA degradation or translation repression modestly; thus, the net effect of miR-466l's binding to IL-10 AU-rich elements is to prevent IL-10 mRNA degradation mediated by tristetraprolin, resulting in extended t1/2 of IL-10 mRNA and elevated IL-10 expression. Thus, competitive binding with RBP to the same target mRNA and subsequent stabilization of target mRNA is an alternative mechanism for gene regulation by miRNAs. Also, a mechanism for regulation of IL-10 by miRNAs is outlined. Copyright © 2010 by The American Association of Immunologists, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/129499
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549
ISI Accession Number ID
Funding AgencyGrant Number
National Key Basic Research Program of China2007CB512403
2009CB521902
National Natural Science Foundation of China30721091
30710302
National High Biotechnology Development Program of China2009ZX09503-003
Shanghai Committee of Science and Technology06DJ14011
Funding Information:

This work was supported by grants from the National Key Basic Research Program of China (2007CB512403, 2009CB521902), National Natural Science Foundation of China (30721091, 30710302), National High Biotechnology Development Program of China (2009ZX09503-003), and Shanghai Committee of Science and Technology (06DJ14011).

References

 

DC FieldValueLanguage
dc.contributor.authorMa, Fen_HK
dc.contributor.authorLiu, Xen_HK
dc.contributor.authorLi, Den_HK
dc.contributor.authorWang, Pen_HK
dc.contributor.authorLi, Nen_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorCao, Xen_HK
dc.date.accessioned2010-12-23T08:38:09Z-
dc.date.available2010-12-23T08:38:09Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Immunology, 2010, v. 184 n. 11, p. 6053-6059en_HK
dc.identifier.issn0022-1767en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129499-
dc.description.abstractMicroRNAs (miRNAs) are generally recognized as regulating gene expression posttranscriptionally by inhibiting translation or inducing target mRNA degradation. New mechanisms for miRNAs to regulate gene expression also still attract much attention. More and more novel miRNAs are discovered by the advanced sequencing technology, but yet their biological functions are largely unknown. Up to now, the function of miR-466l, a miRNA discovered in mouse embryonic stem cells, remains unclear. In this study, we report that miR-466l can upregulate both mRNA and protein expression of IL-10 in TLR-triggered macrophages. Furthermore, we show that miR-466l can competitively bind to the IL-10 3′ untranslated region AU-rich elements, which is a typical binding site for RNA-binding protein (RBP). Tristetraprolin is a well-known RBP, and mediates rapid degradation of IL-10 mRNA. miRNA always mediates target mRNA degradation or translation repression modestly; thus, the net effect of miR-466l's binding to IL-10 AU-rich elements is to prevent IL-10 mRNA degradation mediated by tristetraprolin, resulting in extended t1/2 of IL-10 mRNA and elevated IL-10 expression. Thus, competitive binding with RBP to the same target mRNA and subsequent stabilization of target mRNA is an alternative mechanism for gene regulation by miRNAs. Also, a mechanism for regulation of IL-10 by miRNAs is outlined. Copyright © 2010 by The American Association of Immunologists, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_HK
dc.relation.ispartofJournal of Immunologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGene Expression Regulation - geneticsen_HK
dc.subject.meshImmunoblottingen_HK
dc.subject.meshImmunoprecipitationen_HK
dc.subject.meshInterleukin-10 - biosynthesis - genetics - metabolismen_HK
dc.subject.meshMacrophage Activation - genetics - immunologyen_HK
dc.subject.meshMacrophages - immunologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMicroRNAs - geneticsen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshRNA Processing, Post-Transcriptionalen_HK
dc.subject.meshRNA Stability - geneticsen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshToll-Like Receptors - immunologyen_HK
dc.subject.meshTristetraprolin - metabolismen_HK
dc.subject.meshUp-Regulationen_HK
dc.titleMicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1550-6606 (Electronic)0022-1767 (Linkin&volume=184&issue=11&spage=6053&epage=9&date=2010&atitle=MicroRNA-466l+upregulates+IL-10+expression+in+TLR-triggered+macrophages+by+antagonizing+RNA-binding+protein+tristetraprolin-mediated+IL-10+mRNA+degradationen_US
dc.identifier.emailLu, L:liweilu@hkucc.hku.hken_HK
dc.identifier.authorityLu, L=rp00477en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4049/jimmunol.0902308en_HK
dc.identifier.pmid20410487en_HK
dc.identifier.scopuseid_2-s2.0-77953411618en_HK
dc.identifier.hkuros176949en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953411618&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume184en_HK
dc.identifier.issue11en_HK
dc.identifier.spage6053en_HK
dc.identifier.epage6059en_HK
dc.identifier.eissn1550-6606-
dc.identifier.isiWOS:000278439600017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.citeulike7424688-

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