Tosar Leandro Julian Martinez, Thomas Maria Gabriela, Baez Maria Veronica, Ibanez Irene, Chernomoretz Ariel, Boccaccio Graciela Lidia
Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, Buenos Aires, Argentina.
Front Biosci (Schol Ed). 2012 Jan 1;4(2):432-52. doi: 10.2741/s277.
Staufen is a double-stranded RNA-binding protein that forms RNA granules by RNA-dependent and -independent interactions. Staufen was initially described in Drosophila as a key molecule for targeting maternal mRNAs. In vertebrates, two highly similar paralogs with several splicing variants mediate mRNA transport, thus affecting neuron plasticity, learning and memory. Staufen also regulates translation and mRNA decay. 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.
Staufen是一种双链RNA结合蛋白，通过依赖RNA和不依赖RNA的相互作用形成RNA颗粒。Staufen最初在果蝇中被描述为靶向母体mRNA的关键分子。在脊椎动物中，两个高度相似的旁系同源物及其多个剪接变体介导mRNA运输，从而影响神经元可塑性、学习和记忆。Staufen还调节翻译和mRNA降解。近年来，Staufen被证明是应激颗粒（SGs）的重要调节成分，应激颗粒是在急性细胞应激时特异性诱导形成的沉默mRNP的大聚集体。应激颗粒通过重新编程翻译和抑制促凋亡途径来促进细胞存活，而Staufen似乎通过多种机制对应激颗粒的形成产生负调节作用。最近，在与含有亨廷顿蛋白、TDP43、FUS/TLS或FMRP的应激颗粒相关的RNA颗粒和病理性细胞质聚集体中发现了哺乳动物Staufen。此外，Staufen与导致退行性疾病的突变RNA中存在的CUG重复序列结合，从而改善疾病。最后，Staufen在多个水平上影响HIV和流感感染。总的来说，这些观察结果揭示了Staufen介导的转录后调控在越来越多人类疾病中的重要作用。
