title: 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 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.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA.
authors.forename: Milica
authors.initials: M
authors.lastname: Vukmirovic
authors.forename: Zarko
authors.initials: Z
authors.lastname: Manojlovic
authors.forename: Branko
authors.initials: B
authors.lastname: Stefanovic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D000097585:SS-B Antigen
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; D024042:Collagen Type I; D039601:Eukaryotic Initiation Factor-4A; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C403447:STRAP protein, human; C116758:STRAP protein, mouse
references.citation: Mol Cell Biol. 2000 May;20(9):3157-67
references.pmid: 10757800
references.citation: RNA. 2012 Feb;18(2):321-34
references.pmid: 22190748
references.citation: J Clin Immunol. 2005 Nov;25(6):592-603
references.pmid: 16380822
references.citation: J Biol Chem. 1996 Aug 30;271(35):21566-73
references.pmid: 8702943
references.citation: J Mol Biol. 2010 Jan 15;395(2):309-26
references.pmid: 19917293
references.citation: Mol Cell Biol. 1999 Jun;19(6):4334-42
references.pmid: 10330174
references.citation: Gastroenterology. 2004 Oct;127(4):1260-2
references.pmid: 15481004
references.citation: Matrix Biol. 2004 Oct;23(6):353-61
references.pmid: 15533756
references.citation: Hum Mol Genet. 2005 Oct 15;14(20):3099-111
references.pmid: 16159890
references.citation: Expert Rev Gastroenterol Hepatol. 2009 Feb;3(1):1-3
references.pmid: 19210106
references.citation: Proc Natl Acad Sci U S A. 1977 Mar;74(3):902-5
references.pmid: 265584
references.citation: Br J Haematol. 2008 Apr;141(1):32-5
references.pmid: 18324963
references.citation: Nat Rev Endocrinol. 2011 Jun 14;7(9):540-57
references.pmid: 21670757
references.citation: J Biol Chem. 2002 May 17;277(20):18229-37
references.pmid: 11889120
references.citation: Connect Tissue Res. 2012;53(3):187-96
references.pmid: 22329637
references.citation: Electrophoresis. 2000 Apr;21(6):1037-53
references.pmid: 10786879
references.citation: Semin Cell Dev Biol. 1999 Oct;10(5):455-64
references.pmid: 10597628
references.citation: J Biol Chem. 1999 Jan 22;274(4):2532-8
references.pmid: 9891025
references.citation: Biol Cell. 2003 May-Jun;95(3-4):141-56
references.pmid: 12867079
references.citation: J Am Chem Soc. 1996;118(49):12261-12266
references.pmid: 21451735
references.citation: Nucleic Acids Res. 1983 Mar 11;11(5):1475-89
references.pmid: 6828386
references.citation: Matrix Biol. 1998 Feb;16(7):357-68
references.pmid: 9524356
references.citation: Methods Mol Biol. 1999;112:341-52
references.pmid: 10027260
references.citation: Chest. 1991 Mar;99(3 Suppl):81S-84S
references.pmid: 1997286
references.citation: Mol Cell Biol. 2011 Sep;31(18):3773-89
references.pmid: 21746880
references.citation: Nucleic Acids Res. 2000 Jan 15;28(2):641-7
references.pmid: 10606666
references.citation: J Biol Chem. 2009 May 22;284(21):14609-17
references.pmid: 19321448
references.citation: Annu Rev Biochem. 2009;78:929-58
references.pmid: 19344236
references.citation: Mol Cell. 2009 Dec 25;36(6):1007-17
references.pmid: 20064466
references.citation: Am J Physiol Gastrointest Liver Physiol. 2000 Sep;279(3):G471-6
references.pmid: 10960344
references.citation: Mol Cell Biol. 1997 Sep;17(9):5201-9
references.pmid: 9271398
references.citation: Genes Dev. 1999 Feb 15;13(4):437-48
references.pmid: 10049359
references.citation: Cancer Res. 2006 Jun 15;66(12):6156-66
references.pmid: 16778189
references.citation: Proc Natl Acad Sci U S A. 1988 Feb;85(4):1105-8
references.pmid: 3422482
references.citation: Annu Rev Biochem. 1999;68:913-63
references.pmid: 10872469
references.citation: J Mol Biol. 1987 Aug 20;196(4):947-50
references.pmid: 3681984
references.citation: J Biol Chem. 1989 Mar 5;264(7):3884-9
references.pmid: 2645282
references.citation: J Mol Biol. 2010 Aug 27;401(4):564-78
references.pmid: 20603131
references.citation: J Biol Chem. 1983 Dec 25;258(24):14914-9
references.pmid: 6689169
references.citation: PLoS One. 2012;7(8):e42989
references.pmid: 22900077
references.citation: Mol Cell Biol. 2004 Feb;24(4):1758-68
references.pmid: 14749390
references.citation: Annu Rev Biochem. 2002;71:375-403
references.pmid: 12045101
references.citation: EMBO J. 1997 Nov 17;16(22):6694-701
references.pmid: 9362484
references.citation: Cell Signal. 2010 Jan;22(1):138-49
references.pmid: 19781628
references.citation: Proteomics. 2004 Dec;4(12):3665-85
references.pmid: 15543535
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14
references.pmid: 9482916
references.citation: Mol Cell Biol. 1995 Mar;15(3):1769-77
references.pmid: 7862166
references.citation: Mol Cell Biol. 1995 Oct;15(10):5777-88
references.pmid: 7565731
references.citation: J Dermatol. 1994 Apr;21(4):219-22
references.pmid: 8056893
references.citation: Electrophoresis. 2002 Jul;23(14):2247-51
references.pmid: 12210229
references.citation: Methods Mol Med. 2005;117:141-60
references.pmid: 16130231
references.citation: Nat Rev Mol Cell Biol. 2010 Feb;11(2):113-27
references.pmid: 20094052
references.citation: J Biol Chem. 2003 Jan 10;278(2):927-33
references.pmid: 12419812
references.citation: Nat Genet. 2004 Mar;36(3):304-12
references.pmid: 14981515
references.citation: Mutagenesis. 2003 May;18(3):277-82
references.pmid: 12714694
references.citation: Adv Drug Deliv Rev. 2003 Nov 28;55(12):1531-46
references.pmid: 14623400
references.citation: Matrix Biol. 1994 Apr;14(3):251-62
references.pmid: 7921542