Oct 30, 2004

RNA-binding proteins heterogeneous nuclear ribonucleoprotein A1, E1, and K are involved in post-transcriptional control of collagen I and III synthesis

Circulation Research
B J ThieleV Regitz-Zagrosek

Abstract

Collagen types I and III, coded by COL1A1/COL1A2 and COL3A1 genes, are the major fibrillar collagens produced by fibroblasts, including cardiac fibroblasts of the adult heart. Characteristic for different cardiomyopathies is a remodeling process associated with an upregulation of collagen synthesis, which leads to fibrosis. We report identification of three mRNA-binding proteins, heterogeneous nuclear ribonucleoprote (hnRNP) A1, E1, and K, as positive effectors of collagen synthesis acting at the post-transcriptional level by interaction with the 3'-untranslated regions (3'-UTRs) of COL1A1, 1A2, and 3A1 mRNAs. In vitro, binding experiments (electromobility shift assay and UV cross-linking) reveal significant differences in binding to CU- and AU-rich binding motifs. Reporter gene cell transfection experiments and RNA stability assays show that hnRNPs A1, E1, and K stimulate collagen expression by stabilizing mRNAs. Collagen synthesis is activated via the angiotensin II type 1 (AT1) receptor. We demonstrate that transforming growth factor-beta1, a major product of stimulated AT1 receptor, does not activate solely collagen synthesis but synergistically the synthesis of hnRNP A1, E1, and K as well. Thus, post-transcriptional contro...Continue Reading

Mentioned in this Paper

Cardiomyopathy, Familial Idiopathic
Recombinant Transforming Growth Factor
Heterogeneous Nuclear Ribonucleoprotein A1
Heterogeneous nuclear ribonucleoprotein A2-B1
Transforming Growth Factor beta
Transfection
Untranslated Regions
Specimen Type - Fibroblasts
TGFB1 protein, human
Post-Transcriptional Regulation

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