Previous Article | Next Article ![]()
Molecular and Cellular Biology, June 1999, p. 4334-4342, Vol. 19, No. 6
Departments of Medicine and Biochemistry and
Biophysics, University of North Carolina at Chapel Hill, Chapel
Hill, North Carolina
Received 1 June 1998/Returned for modification 1 October
1998/Accepted 17 March 1999
Three fibrillar collagen mRNAs,
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Regulatory Role of the Conserved Stem-Loop
Structure at the 5' End of Collagen
1(I) mRNA
1(I),
2(I), and
1(III),
are coordinately upregulated in the activated hepatic stellate cell
(hsc) in liver fibrosis. These three mRNAs contain sequences surrounding the start codon that can be folded into a stem-loop structure. We investigated the role of this stem-loop structure in
expression of collagen
1(I) reporter mRNAs in hsc's and
fibroblasts. The stem-loop dramatically decreases accumulation of mRNAs
in quiescent hsc's and to a lesser extent in activated hsc's and fibroblasts. The stem-loop decreases mRNA stability in fibroblasts. In
activated hsc's and fibroblasts, a protein complex binds to the
stem-loop, and this binding requires the presence of a 7mG cap on the
RNA. Placing the 3' untranslated region (UTR) of collagen
1(I) mRNA
in a reporter mRNA containing this stem-loop further increases the
steady-state level in activated hsc's. This 3' UTR binds
CP, a
protein implicated in increasing stability of collagen
1(I) mRNA in
activated hsc's (B. Stefanovic, C. Hellerbrand, M. Holcik, M. Briendl,
S. A. Liebhaber, and D. A. Brenner, Mol. Cell. Biol.
17:5201-5209, 1997). A set of protein complexes assembles on the 7mG
capped stem-loop RNA, and a 120-kDa protein is specifically cross-linked to this structure. Thus, collagen
1(I) mRNA is
regulated by a complex interaction between the 5' stem-loop and the 3'
UTR, which may optimize collagen production in activated hsc's.
*
Corresponding author. Mailing address: University of
North Carolina at Chapel Hill, Division of Digestive Diseases and
Nutrition, CB 7038, 154 Glaxo Building, Chapel Hill, NC 27599. Phone:
(919) 966-7885. Fax: (919) 966-7468. E-mail:
cjc8{at}med.unc.edu.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|