Serine-threonine kinase receptor-associated protein (STRAP) regulates translation of type I collagen mRNAs.

ABSTRACT: Type I collagen is the most abundant protein in the human body and is composed of two ?1(I) and one ?2(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 ?1(I) and ?2(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 ?2(I) mRNAs, by interacting with eukaryotic translation initiation factor 4A (eIF4A). In the absence of STRAP, more collagen ?2(I) mRNA can be pulled down with eIF4A, and collagen ?2(I) mRNA is unrestrictedly loaded onto the polysomes. This results in an imbalance of synthesis of ?1(I) and ?2(I) polypeptides, in hypermodifications of ?1(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.

SUBMITTER: Vukmirovic M 

PROVIDER: S-EPMC3811873 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other