TL;DR: The data demonstrate that the NC1 and COL1 domains of type XII collagen contain the information necessary for trimer formation and that, contrary to the fibrillar collagen types, posttranslational modification of the triple helical domain is essential for assembly and disulfide bonding of the chains.
TL;DR: The results indicate that the 5′ stem-loop specifically regulates fibrillar collagen synthesis and represents a novel target for antifibrotic therapy as well as a generalized method of assessing the functional significance of blocking the interactions of mRNA and proteins.
TL;DR: It is shown that serine-threonine kinase receptor-associated protein (STRAP) is tethered to collagen mRNAs by interaction with LARP6, a protein which directly binds the 5′ stem-loop present in collagen α1(I) and α2(I), and STRAP is discovered as a novel regulator of the coordinated translation of collagen m RNAs.
Abstract: Type I collagen is the most abundant protein in the human body and is composed of two α1(I) and one α2(I) polypeptides which assemble into a triple helix. For the proper assembly of the collagen triple helix, the individual polypeptides must be translated in coordination. Here, we show that serine-threonine kinase receptor-associated protein (STRAP) is tethered to collagen mRNAs by interaction with LARP6. LARP6 is a protein which directly binds the 5' stem-loop (5'SL) present in collagen α1(I) and α2(I) mRNAs, but it interacts with STRAP with its C-terminal domain, which is not involved in binding 5'SL. Being tethered to collagen mRNAs, STRAP prevents unrestricted translation, primarily that of collagen α2(I) mRNAs, by interacting with eukaryotic translation initiation factor 4A (eIF4A). In the absence of STRAP, more collagen α2(I) mRNA can be pulled down with eIF4A, and collagen α2(I) mRNA is unrestrictedly loaded onto the polysomes. This results in an imbalance of synthesis of α1(I) and α2(I) polypeptides, in hypermodifications of α1(I) polypeptide, and in inefficient assembly of the polypeptides into a collagen trimer and their secretion as monomers. These defects can be partially restored by supplementing STRAP. Thus, we discovered STRAP as a novel regulator of the coordinated translation of collagen mRNAs.
TL;DR: It is hypothesized that the interaction of collagen type I trimer fibrils with tumour cells is instrumental in augmenting tumour cell progression and that the trimer may provide contact guidance for invasive growth.
Abstract: The tumour stroma in cases of ductal infiltrating carcinoma of the mammary gland contains substantial amounts of collagen type I trimer, besides the regular collagen types. Reconstituted collagen trimer consists of fibrils that are significantly thinner than reconstituted fibrils of type I collagen. The axial periodicity is somewhat longer due to widening of the c-d and d-e regions. Transmission EM of the tumours shows characteristic phenomena at the stromal-tumour cell junctions: frequent absence of a basal lamina and thin disordered collagen fibrils that show frequent direct contacts with tumour cells. On the basis of literature data concerning the interaction between stroma and epithelia under physiological and pathological conditions it is hypothesized that the interaction of collagen type I trimer fibrils with tumour cells is instrumental in augmenting tumour cell progression and that the trimer may provide contact guidance for invasive growth.
TL;DR: Findings support the proposal that the lysine overhydroxylation resulted from a perturbation of helix propagation from the COOH to NH2 terminus of the collagen trimer caused by the structural defect in alpha 1(I)CB7.