Biochemical Society Transactions

677th Meeting

Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover

P. J. Blackshear


The tristetraprolin (TTP) family of CCCH tandem zinc-finger proteins is composed of three known members in mammals, with a fourth member recently identified in frogs and fish. Although TTP was first cloned more than 10 years ago as a growth factor-induced gene, a physiological function for the protein has been discovered only within the last few years. TTP is now known to bind to so-called class II AU-rich elements within the mRNAs that encode tumour necrosis factor-α and granulocyte/macrophage colony-stimulating factor. In both cases, this binding results in destabilization of the mRNA and decreased secretion of the protein. Recent evidence suggests that TTP can accomplish this accelerated mRNA degradation by first promoting removal of the polyadenylated tail from the mRNA (deadenylation). In functional assays in cells, the other family members have similar activities, but are expressed differently in tissues and in response to stimuli, suggesting that they may control the stability of mRNAs under different circumstances from those in which TTP affects mRNA. All of these proteins are phosphoproteins and nucleo-cytoplasmic shuttling proteins, suggesting that their activities can be regulated in ways other than regulating gene transcription. Together, the TTP family members should be capable of complex regulation of short-lived mRNAs containing this type of AU-rich instability motif.

  • AU-rich element
  • cytokine
  • deadenylation
  • ARE, AU-rich element
  • BRF, butyrate-response factor
  • ERF, EGF-response factor
  • GM-CSF, granulocyte/macrophage colony-stimulating factor
  • GOS24, G0/G1 switch regulatory gene 24
  • KO, knockout
  • LPS, lipopolysaccharide
  • MAP, mitogen-activated protein
  • NUP475, nuclear protein 475
  • poly(A)+, polyadenylated
  • TISII, TPA-induced sequence II
  • TNF, tumour necrosis factor
  • TTP, tristetraprolin
  • WT, wild-type
  • ZFP, zinc-finger protein