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

Int J Mol Sci. 2016 Mar 22;17(3):419. doi: 10.3390/ijms17030419.

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.

Keywords: LARP6; collagen mRNA binding protein; collagen mRNA translation; posttranscriptional regulation; ribonucleoprotein complexes; type I collagen.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Collagen Type I / genetics*
  • Collagen Type I / metabolism
  • Humans
  • Protein Binding
  • RNA Processing, Post-Transcriptional*
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*

Substances

  • Autoantigens
  • Collagen Type I
  • RNA, Messenger
  • Ribonucleoproteins
  • SS-B antigen