hnRNP F complexes with tristetraprolin and stimulates ARE-mRNA decay

PLoS One. 2014 Jun 30;9(6):e100992. doi: 10.1371/journal.pone.0100992. eCollection 2014.

Abstract

The tristetraprolin (TTP) family of zinc-finger proteins, TTP, BRF1 and BRF2, regulate the stability of a subset of mRNAs containing 3'UTR AU-rich elements (AREs), including mRNAs coding for cytokines, transcription factors, and proto-oncogenes. To better understand the mechanism by which TTP-family proteins control mRNA stability in mammalian cells, we aimed to identify TTP- and BRF1-interacting proteins as potential TTP-family co-factors. This revealed hnRNP F as a prominent interactor of TTP and BRF1. While TTP, BRF1 and hnRNP F are all RNA binding proteins (RBPs), the interaction of hnRNP F with TTP and BRF1 is independent of RNA. Depletion of hnRNP F impairs the decay of a subset of TTP-substrate ARE-mRNAs by a mechanism independent of the extent of hnRNP F binding to the mRNA. Taken together, these findings implicate hnRNP F as a co-factor in a subset of TTP/BRF-mediated mRNA decay and highlight the importance of RBP cooperativity in mRNA regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Animals
  • Cell Line
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Genes, Reporter
  • HEK293 Cells
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / antagonists & inhibitors
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / metabolism*
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism
  • Mice
  • NIH 3T3 Cells
  • RNA Stability
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • TATA-Binding Protein Associated Factors / genetics
  • TATA-Binding Protein Associated Factors / metabolism*
  • Transcription Factor TFIIIB / genetics
  • Transcription Factor TFIIIB / metabolism*
  • Tristetraprolin / genetics
  • Tristetraprolin / metabolism*

Substances

  • 3' Untranslated Regions
  • BRF1 protein, human
  • BRF2 protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H
  • RNA, Small Interfering
  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIIIB
  • Tristetraprolin
  • ZFP36 protein, human
  • Luciferases