A novel role of vimentin filaments: binding and stabilization of collagen mRNAs
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Ημερομηνία
Συγγραφείς
Τίτλος Εφημερίδας
Περιοδικό ISSN
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Εκδότης
Περίληψη
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Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Mol Cell Biol
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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.
Περιγραφή
Λέξεις-κλειδιά
5' Untranslated Regions, Animals, Autoantigens/genetics/*metabolism, Cell Line, Collagen Type I/biosynthesis/*genetics/metabolism, Desmin/biosynthesis, Fibroblasts/metabolism, Fibrosis/genetics/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/*metabolism, RNA, Small Interfering, RNA-Binding Proteins/genetics/metabolism, Ribonucleoproteins/genetics/*metabolism, Vimentin/genetics/*metabolism
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/21746880
http://mcb.asm.org/content/31/18/3773.full.pdf
http://mcb.asm.org/content/31/18/3773.full.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής