The double-stranded RNA-binding protein STAUFEN: From embryo polarity to the stress response and neurodegeneration

MARTINEZ TOSAR L.J; THOMAS M. G.; BAEZ, M.V.; IBAÑEZ I.; CHERNOMORETZ A.; BOCCACCIO L.

FRONTIERS IN BIOSCIENCE-LANDMARK

FRONTIERS IN BIOSCIENCE INC

Lugar: Albertson, NY; Año: 2012 p. 432 - 452

1093-9946

<!-- @page { margin: 0.79in } P { margin-bottom: 0.08in } --> Staufen is a double stranded-RNA binding protein that forms RNA granules by means of RNA-dependent and -independent intermolecular interactions. Staufen was initially described in Drosophila as a key molecule for targeting maternal mRNAs in the developing embryo. In vertebrates, two highly similar paralogs with several splicing variants mediate mRNA transport in neurons, thus affecting plasticity, learning and memory. In addition, a role for Staufen in translation activation and mRNA decay is apparent. In recent years, Staufen was shown to be an important regulatory component of stress granules (SGs), which are large aggregates of silenced mRNPs specifically induced upon acute cellular stress. SGs contribute to cell survival by reprogramming translation and inhibiting pro-apoptotic pathways and Staufen appears to negatively modulate SG formation by several mechanisms. More recently, mammalian Staufen was found in RNA granules and pathological cytoplasmic aggregates related to SGs containing huntingtin, TDP43, FUS/TLS or FMRP. In addition, Staufen binds CUG repeats present in mutant RNAs causative of degenerative conditions, thus ameliorating disease. Finally, Staufen affects HIV and influenza infection at several levels. Collectively, these observations unveil important roles for Staufen-mediated post-transcriptional regulation in a growing number of human diseases.