A novel role of vimentin filaments: binding and stabilization of collagen mRNAs

Απλή σελίδα τεκμηρίου
dc.contributor.authorChalla, A. A.en
dc.contributor.authorStefanovic, B.en
dc.date.accessioned2015-11-24T19:40:03Z
dc.date.available2015-11-24T19:40:03Z
dc.identifier.issn1098-5549-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/24293
dc.rightsDefault Licence-
dc.subject5' Untranslated Regionsen
dc.subjectAnimalsen
dc.subjectAutoantigens/genetics/*metabolismen
dc.subjectCell Lineen
dc.subjectCollagen Type I/biosynthesis/*genetics/metabolismen
dc.subjectDesmin/biosynthesisen
dc.subjectFibroblasts/metabolismen
dc.subjectFibrosis/genetics/metabolismen
dc.subjectGene Knock-In Techniquesen
dc.subjectGene Knockout Techniquesen
dc.subjectHEK293 Cellsen
dc.subjectHumansen
dc.subjectIn Situ Hybridizationen
dc.subjectIntermediate Filaments/*metabolismen
dc.subjectInverted Repeat Sequencesen
dc.subjectMiceen
dc.subjectMice, Knockouten
dc.subjectNucleic Acid Conformationen
dc.subjectPolymerase Chain Reactionen
dc.subjectRNA Interferenceen
dc.subjectRNA, Messenger/*genetics/*metabolismen
dc.subjectRNA, Small Interferingen
dc.subjectRNA-Binding Proteins/genetics/metabolismen
dc.subjectRibonucleoproteins/genetics/*metabolismen
dc.subjectVimentin/genetics/*metabolismen
dc.titleA novel role of vimentin filaments: binding and stabilization of collagen mRNAsen
heal.abstractThe stem-loop in the 5' untranslated region (UTR) of collagen alpha1(I) and alpha2(I) mRNAs (5'SL) is the key element regulating their stability and translation. Stabilization of collagen mRNAs is the predominant mechanism for high collagen expression in fibrosis. LARP6 binds the 5'SL of alpha1(I) and alpha2(I) mRNAs with high affinity. Here, we report that vimentin filaments associate with collagen mRNAs in a 5'SL- and LARP6-dependent manner and stabilize collagen mRNAs. LARP6 interacts with vimentin filaments through its La domain and colocalizes with the filaments in vivo. Knockdown of LARP6 by small interfering RNA (siRNA) or mutation of the 5'SL abrogates the interaction of collagen mRNAs with vimentin filaments. Vimentin knockout fibroblasts produce reduced amounts of type I collagen due to decreased stability of collagen alpha1(I) and alpha2(I) mRNAs. Disruption of vimentin filaments using a drug or by expression of dominant-negative desmin reduces type I collagen expression, primarily due to decreased stability of collagen mRNAs. RNA fluorescence in situ hybridization (FISH) experiments show that collagen alpha1(I) and alpha2(I) mRNAs are associated with vimentin filaments in vivo. Thus, vimentin filaments may play a role in the development of tissue fibrosis by stabilizing collagen mRNAs. This finding will serve as a rationale for targeting vimentin in the development of novel antifibrotic therapies.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1128/MCB.05263-11-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/21746880-
heal.identifier.secondaryhttp://mcb.asm.org/content/31/18/3773.full.pdf-
heal.journalNameMol Cell Biolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2011-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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