Department of Molecular Biology, CIMH and Medical Faculty Mannheim, Heidelberg University, 68159, Mannheim, Germany.
Division of Neurosciences, Pablo de Olavide University, 41013, Seville, Spain.
Genome Biol. 2017 Nov 17;18(1):222. doi: 10.1186/s13059-017-1350-8.
Dendritic messenger RNA (mRNA) localization and subsequent local translation in dendrites critically contributes to synaptic plasticity and learning and memory. Little is known, however, about the contribution of RNA-binding proteins (RBPs) to these processes in vivo.
To delineate the role of the double-stranded RBP Staufen2 (Stau2), we generate a transgenic rat model, in which Stau2 expression is conditionally silenced by Cre-inducible expression of a microRNA (miRNA) targeting Stau2 mRNA in adult forebrain neurons. Known physiological mRNA targets for Stau2, such as RhoA, Complexin 1, and Rgs4 mRNAs, are found to be dysregulated in brains of Stau2-deficient rats. In vivo electrophysiological recordings reveal synaptic strengthening upon stimulation, showing a shift in the frequency-response function of hippocampal synaptic plasticity to favor long-term potentiation and impair long-term depression in Stau2-deficient rats. These observations are accompanied by deficits in hippocampal spatial working memory, spatial novelty detection, and in tasks investigating associative learning and memory.
Together, these experiments reveal a critical contribution of Stau2 to various forms of synaptic plasticity including spatial working memory and cognitive management of new environmental information. These findings might contribute to the development of treatments for conditions associated with learning and memory deficits.
树突信使 RNA（mRNA）在树突中的定位和随后的局部翻译对突触可塑性和学习记忆至关重要。然而，关于 RNA 结合蛋白（RBPs）在体内对这些过程的贡献知之甚少。
为了描绘双链 RBP 司塔夫 2（Stau2）的作用，我们生成了一种转基因大鼠模型，其中 Stau2 的表达通过 Cre 诱导的针对 Stau2 mRNA 的 microRNA（miRNA）的表达而被条件沉默。已知 Stau2 的生理 mRNA 靶标，如 RhoA、Complexin 1 和 Rgs4 mRNAs，在 Stau2 缺陷型大鼠的大脑中被失调。体内电生理记录显示刺激后的突触增强，显示海马突触可塑性的频率响应函数发生转变，有利于长时程增强，损害 Stau2 缺陷型大鼠的长时程抑制。这些观察结果伴随着海马体空间工作记忆、空间新颖性检测以及与联想学习和记忆相关的任务中的缺陷。
总之，这些实验揭示了 Stau2 对各种形式的突触可塑性的关键贡献，包括空间工作记忆和对新环境信息的认知管理。这些发现可能有助于开发与学习和记忆缺陷相关的治疗方法。
