A single element in the 3'UTR of the apical sodium-dependent bile acid transporter controls both stabilization and destabilization of mRNA

Biochem J. 2014 Sep 15;462(3):547-53. doi: 10.1042/BJ20140070.


mRNA stability appears to play a key role in the ontogenic regulation of the apical sodium-dependent bile acid transporter (ASBT). The RNA-binding proteins Hu antigen R (HuR) and tristetraprolin (TTP) stabilize and destabilize ASBT mRNA, respectively. Potential HuR-binding sites were assessed by sequence analysis in the context of prior in vitro functional analyses of the rat ASBT 3'UTR. Wild-type and mutant-binding sites were investigated by gel-shift analysis using IEC-6 cell extracts. The functional consequences of binding site mutations were assessed using two different hybrid reporter constructs linking the 3'UTR element to either a luciferase or a β-globin coding mRNA sequence. A specific metastasis-associated gene 1 (MTA1) cis-element was identified in the ASBT 3'UTR that became associated with proteins in IEC-6 cell extracts and could be supershifted by anti-HuR or anti-TTP antibodies. Mutation of this cis-element abrogated the gel shift of IEC-6 proteins. Furthermore, hybrid constructs containing a mutant MTA1 element had reduced responses to modulation of HuR or TTP. For the first time, we have identified a single specific sequence element in the 3'UTR of the rat ASBT mRNA that mediates counter-regulatory changes in mRNA abundance in response to both HuR and TTP.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Animals
  • Binding Sites
  • ELAV Proteins / genetics*
  • ELAV Proteins / metabolism
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • Proteins / genetics
  • Proteins / physiology*
  • RNA Stability / genetics*
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics
  • Rats
  • Symporters / genetics*
  • Tristetraprolin / metabolism


  • 3' Untranslated Regions
  • ELAV Proteins
  • Mta1 protein, rat
  • Organic Anion Transporters, Sodium-Dependent
  • Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Symporters
  • Tristetraprolin
  • sodium-bile acid cotransporter