LARP6 Meets Collagen mRNA: Specific Regulation of Type I Collagen Expression

Abstract

Type I collagen is the most abundant structural protein in all vertebrates, but its constitutive rate of synthesis is low due to long half-life of the protein (60–70 days). However, several hundred fold increased production of type I collagen is often seen in reparative or reactive fibrosis. The mechanism which is responsible for this dramatic upregulation is complex, including multiple levels of regulation. However, posttranscriptional regulation evidently plays a predominant role. Posttranscriptional regulation comprises processing, transport, stabilization and translation of mRNAs and is executed by RNA binding proteins. There are about 800 RNA binding proteins, but only one, La ribonucleoprotein domain family member 6 (LARP6), is specifically involved in type I collagen regulation. In the 5′untranslated region (5’UTR) of mRNAs encoding for type I and type III collagens there is an evolutionally conserved stem-loop (SL) structure; this structure is not found in any other mRNA, including any other collagen mRNA. LARP6 binds to the 5′SL in sequence specific manner to regulate stability of collagen mRNAs and their translatability. Here, we will review current understanding of how is LARP6 involved in posttranscriptional regulation of collagen mRNAs. We will also discuss how other proteins recruited by LARP6, including nonmuscle myosin, vimentin, serine threonine kinase receptor associated protein (STRAP), 25 kD FK506 binding protein (FKBP25) and RNA helicase A (RHA), contribute to this process.

Insulin‐like growth factor‐1 promotes osteogenic differentiation and collagen I alpha 2 synthesis via induction of mRNA‐binding protein LARP6 expression

“…Posttranscriptional regulation involves stabilization of collagen mRNAs and regulation of their translation, and is mediated by LARP6 and another RNA‐binding protein, α CP (Bayfield et al . ; Stefanovic ; Zhang & Stefanovic ), our study also showed that LARP6 protein can bind to Col1a2 mRNA (Fig. e, f).…”

“…ª 2017 Japanese Society of Developmental Biologists 2013; Zhang & Stefanovic 2016), our study also showed that LARP6 protein can bind to Col1a2 mRNA (Fig. 3e, f).…”

“…Posttranscriptional regulation involves the stabilization of collagen mRNAs and regulation of their translation, and is mediated by two RNA binding proteins: α CP (Lindquist et al . ) and La ribonucleoprotein domain family member 6 (LARP6) (Zhang & Stefanovic ).…”

“…Mutations in either of the genes encoding the pro-a1 or pro-a2 chains of type I collagen result in osteogenesis imperfecta, which is characterized by collagen type I synthesis deficiency, and further results in bones that break easily, often from little or no apparent cause (Van Dijk et al 2010). Posttranscriptional regulation involves the stabilization of collagen mRNAs and regulation of their translation, and is mediated by two RNA binding proteins: aCP (Lindquist et al 2004) and La ribonucleoprotein domain family member 6 (LARP6) (Zhang & Stefanovic 2016).…”

ID3 mediates the TGF‐β1‐induced suppression of matrix metalloproteinase‐1 in human granulosa cells

“…Type I collagens are the most abundant component proteins of ECM in human body , and previous studies have shown that Type I collagens account for more than 90% of bone ECM . Type I collagen is a trimeric complex molecule that comprises with two alpha‐1 subunits (COL1A1) and one alpha‐2 subunit (COL1A2) . During the developmental process of growing follicles, collagen content is dynamically changing.…”