PMID- 21746880 OWN - NLM STAT- MEDLINE DCOM- 20111024 LR - 20231213 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 31 IP - 18 DP - 2011 Sep TI - A novel role of vimentin filaments: binding and stabilization of collagen mRNAs. PG - 3773-89 LID - 10.1128/MCB.05263-11 [doi] AB - The 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. FAU - Challa, Azariyas A AU - Challa AA AD - Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA. FAU - Stefanovic, Branko AU - Stefanovic B LA - eng GR - R01 DK059466/DK/NIDDK NIH HHS/United States GR - 5R01DK059466-08/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110711 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (5' Untranslated Regions) RN - 0 (Autoantigens) RN - 0 (Collagen Type I) RN - 0 (Desmin) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (RNA-Binding Proteins) RN - 0 (Ribonucleoproteins) RN - 0 (Vimentin) SB - IM MH - 5' Untranslated Regions MH - Animals MH - Autoantigens/genetics/*metabolism MH - Cell Line MH - Collagen Type I/biosynthesis/*genetics/metabolism MH - Desmin/biosynthesis MH - Fibroblasts/metabolism MH - Fibrosis/genetics/metabolism MH - Gene Knock-In Techniques MH - Gene Knockout Techniques MH - HEK293 Cells MH - Humans MH - In Situ Hybridization MH - Intermediate Filaments/*metabolism MH - Inverted Repeat Sequences MH - Mice MH - Mice, Knockout MH - Nucleic Acid Conformation MH - Polymerase Chain Reaction MH - RNA Interference MH - RNA, Messenger/*genetics/*metabolism MH - RNA, Small Interfering MH - RNA-Binding Proteins/genetics/metabolism MH - Ribonucleoproteins/genetics/*metabolism MH - Vimentin/genetics/*metabolism MH - SS-B Antigen PMC - PMC3165730 EDAT- 2011/07/13 06:00 MHDA- 2011/10/25 06:00 PMCR- 2012/03/01 CRDT- 2011/07/13 06:00 PHST- 2011/07/13 06:00 [entrez] PHST- 2011/07/13 06:00 [pubmed] PHST- 2011/10/25 06:00 [medline] PHST- 2012/03/01 00:00 [pmc-release] AID - MCB.05263-11 [pii] AID - 5263-11 [pii] AID - 10.1128/MCB.05263-11 [doi] PST - ppublish SO - Mol Cell Biol. 2011 Sep;31(18):3773-89. doi: 10.1128/MCB.05263-11. Epub 2011 Jul 11.