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An open reading frame element mediates posttranscriptional regulation of tropoelastin and responsiveness to transforming growth factor beta1.

Abstract：

:Elastin, an extracellular component of arteries, lung, and skin, is produced during fetal and neonatal growth. We reported previously that the cessation of elastin production is controlled by a posttranscriptional mechanism. Although tropoelastin pre-mRNA is transcribed at the same rate in neonates and adults, marked instability of the fully processed transcript bars protein production in mature tissue. Using RNase protection, we identified a 10-nucleotide sequence in tropoelastin mRNA near the 5' end of the sequences coded by exon 30 that interacts specifically with a developmentally regulated cytosolic 50-kDa protein. Binding activity increased as tropoelastin expression dropped, being low in neonatal fibroblasts and high in adult cells, and treatment with transforming growth factor beta1 (TGF-beta1), which stimulates tropoelastin expression by stabilizing its mRNA, reduced mRNA-binding activity. No other region of tropoelastin mRNA interacted with cellular proteins, and no binding activity was detected in nuclear extracts. The ability of the exon-30 element to control mRNA decay and responsiveness to TGF-beta1 was assessed by three distinct functional assays: (i) insertion of exon 30 into a heterologous gene conferred increased reporter activity after exposure to TGF-beta1; (ii) addition of excess exon 30 RNA slowed tropoelastin mRNA decay in an in vitro polysome degradation assay; and (iii) a mutant tropoelastin cDNA lacking exon 30, compared to wild-type cDNA, produced a stable transcript whose levels were not affected by TGF-beta1. These findings demonstrate that posttranscriptional regulation of elastin production in mature tissue is conferred by a specific element within the open reading frame of tropoelastin mRNA.

journal_name

Mol Cell Biol

journal_title

Molecular and cellular biology

authors

Zhang M,Pierce RA,Wachi H,Mecham RP,Parks WC

doi

10.1128/mcb.19.11.7314

subject

Has Abstract

pub_date

1999-11-01 00:00:00

pages

7314-26

issue

eissn

0270-7306

issn

1098-5549

journal_volume

pub_type

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An open reading frame element mediates posttranscriptional regulation of tropoelastin and responsiveness to transforming growth factor beta1.