ABSTRACT 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.
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