Type I collagen is the most abundant protein in human body and its excessive biosynthesis is associated with organ fibrosis. Fibrosis is a major medical problem, but there are no approved antifibrotic drugs. The biosynthesis of type I collagen is complex; however, one molecular interaction in the biosynthetic pathway is unique for type I collagen production and suitable for targeting by drugs. This interaction is binding of RNA-binding protein LARP6 to the specific sequence element of type I collagen mRNAs, the 5’ stem-loop (5’SL). LARP6 binding regulates translation of collagen mRNAs and enables high level of type I collagen production in fibrosis. The importance of LARP6-dependent mechanism has been documented in fibrosis of several organs. This review will describe the peculiar aspects of type I collagen biosynthetic pathway, the mechanism of LARP6 regulation and its evolutionary conservation and the importance of the mechanism for fibrosis development and for the discovery of novel inhibitors.
Buy this Article