Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action

Biochim Biophys Acta. Jun-Jul 2013;1829(6-7):666-79. doi: 10.1016/j.bbagrm.2013.02.003. Epub 2013 Feb 18.

Abstract

Changes in mRNA stability and translation are critical control points in the regulation of gene expression, particularly genes encoding growth factors, inflammatory mediators, and proto-oncogenes. Adenosine and uridine (AU)-rich elements (ARE), often located in the 3' untranslated regions (3'UTR) of mRNAs, are known to target transcripts for rapid decay. They are also involved in the regulation of mRNA stability and translation in response to extracellular cues. This review focuses on one of the best characterized ARE binding proteins, tristetraprolin (TTP), the founding member of a small family of CCCH tandem zinc finger proteins. In this survey, we have reviewed the current status of TTP interactions with mRNA and proteins, and discussed current thinking about TTP's mechanism of action to promote mRNA decay. We also review the proposed regulation of TTP's functions by phosphorylation. Finally, we have discussed emerging evidence for TTP operating as a translational regulator. This article is part of a Special Issue entitled: RNA Decay mechanisms.

Publication types

  • Review

MeSH terms

  • 3' Untranslated Regions
  • AU Rich Elements / genetics*
  • Base Sequence
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • Molecular Sequence Data
  • Protein Biosynthesis*
  • RNA Stability / drug effects
  • RNA Stability / genetics*
  • RNA, Messenger / genetics*
  • Tristetraprolin / genetics*
  • Tristetraprolin / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Zinc Fingers / genetics

Substances

  • 3' Untranslated Regions
  • RNA, Messenger
  • Tristetraprolin
  • Tumor Necrosis Factor-alpha