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novel role of vimentin filaments

Title: A novel role of vimentin filaments: binding and stabilization of collagen mRNAs.
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Name(s): Challa, Azariyas A, author
Stefanovic, Branko, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2011-09-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The stem-loop in the 5' untranslated region (UTR) of collagen α1(I) and α2(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 α1(I) and α2(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 α1(I) and α2(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 α1(I) and α2(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.
Identifier: FSU_pmch_21746880 (IID), 10.1128/MCB.05263-11 (DOI), PMC3165730 (PMCID), 21746880 (RID), 21746880 (EID), MCB.05263-11 (PII)
Grant Number: R01 DK059466, 5R01DK059466-08
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165730.
Subject(s): 5' Untranslated Regions
Animals
Autoantigens/genetics
Autoantigens/metabolism
Cell Line
Collagen Type I/biosynthesis
Collagen Type I/genetics
Collagen Type I/metabolism
Desmin/biosynthesis
Fibroblasts/metabolism
Fibrosis/genetics
Fibrosis/metabolism
Gene Knock-In Techniques
Gene Knockout Techniques
HEK293 Cells
Humans
In Situ Hybridization
Intermediate Filaments/metabolism
Inverted Repeat Sequences
Mice
Mice, Knockout
Nucleic Acid Conformation
Polymerase Chain Reaction
RNA Interference
RNA, Messenger/genetics
RNA, Messenger/metabolism
RNA, Small Interfering
RNA-Binding Proteins/genetics
RNA-Binding Proteins/metabolism
Ribonucleoproteins/genetics
Ribonucleoproteins/metabolism
Vimentin/genetics
Vimentin/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_21746880
Owner Institution: FSU
Is Part Of: Molecular and cellular biology.
1098-5549
Issue: iss. 18, vol. 31

Choose the citation style.
Challa, A. A., & Stefanovic, B. (2011). A novel role of vimentin filaments: binding and stabilization of collagen mRNAs. Molecular And Cellular Biology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_21746880