The zinc-finger protein ZFR is critical for Staufen 2 isoform specific nucleocytoplasmic shuttling in neurons
Article first published online: 8 NOV 2005
Journal of Neurochemistry
Volume 96, Issue 1, pages 105–117, January 2006
How to Cite
Elvira, G., Massie, B. and DesGroseillers, L. (2006), The zinc-finger protein ZFR is critical for Staufen 2 isoform specific nucleocytoplasmic shuttling in neurons. Journal of Neurochemistry, 96: 105–117. doi: 10.1111/j.1471-4159.2005.03523.x
- Issue published online: 8 NOV 2005
- Article first published online: 8 NOV 2005
- Received May 24, 2005; revised manuscript received August 29, 2005; accepted August 31, 2005.
- nuclear localization;
- RNA granule;
- RNA transport
In mammalian neurons, transport and translation of mRNA to individual potentiated synapses is believed to occur via a heterogeneous population of RNA granules. To identify components of Staufen2-containing granules, we used the yeast two-hybrid system. A mouse fetal cDNA library was screened with the N-terminal fragment of Staufen2 as bait. ZFR, a three zinc finger protein, was identified as an interacting protein. Confocal microscopy showed that ZFR, although mainly nuclear, was also found in the somatodendritic compartment of primary hippocampal neurons where it localized as granule-like structures. Co-localization with Staufen2 was observed in several granules. Biochemical analyses (immunoprecipitation, cell fractionation) further confirmed the ZFR/Staufen2 association. ZFR was shown to interact with at least the Staufen262 isoform, but not with Staufen1. ZFR also co-fractionated with ribosomes and Staufen259 and Staufen252 in a sucrose gradient. Interestingly, knockdown expression of ZFR through RNA interference in neurons relocated specifically the Staufen262, but not the Staufen259, isoform to the nucleus. Our results demonstrate that ZFR is a native component of Staufen2-containing granules and likely plays its role during early steps of RNA transport and localization. They also suggest that one of these roles may be linked to Staufen262-containing RNA granule formation in the nucleus and/or to their nucleo-cytoplasmic shuttling.