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