Inoue Masatoshi, Yagishita-Kyo Nan, Nonaka Mio, Kawashima Takashi, Okuno Hiroyuki, Bito Haruhiko
Department of Neurochemistry; University of Tokyo Graduate School of Medicine; Bunkyo-ku, Tokyo Japan.
Commun Integr Biol. 2010 Sep;3(5):443-6. doi: 10.4161/cib.3.5.12287.
Formation of a new memory requires plasticity at the synaptic level. However, it has also been shown that the consolidation and the maintenance of such a new memory involve processes that necessitate active mRNA at the nucleus of the cell. How can robust changes in synaptic efficacy specifically drive new transcription and translation of new gene transcripts, and thus transform an otherwise transient plasticity into a long-lasting and stable one? In this article, we highlight the conceptual advance that was gained by the discovery of a potent Synaptic Activity-Responsive Element (SARE) found ∼7 kb upstream of the transcription initiation site of the neuronal immediate early gene Arc. The unique genomic structure of SARE, which contained adjacent and cooperative binding sites for three major activity-dependent transcription factors within a 100-bp locus, was associated with an unusual responsiveness to neuronal stimuli. Taken together, these findings shed light on a new class of transcriptional sensor with enhanced sensitivity to synaptic activity.
新记忆的形成需要突触水平的可塑性。然而，研究还表明，这种新记忆的巩固和维持涉及一些过程，这些过程需要细胞核对活性mRNA的参与。突触效能的强烈变化如何具体驱动新基因转录本的新转录和翻译，从而将原本短暂的可塑性转化为持久而稳定的可塑性呢？在本文中，我们强调了一项概念上的进展，即发现了一个位于神经元即刻早期基因Arc转录起始位点上游约7 kb处的强大突触活动反应元件（SARE）。SARE独特的基因组结构在一个100 bp的位点内包含三个主要活性依赖转录因子的相邻且协同的结合位点，这与对神经元刺激的异常反应性相关。综上所述，这些发现揭示了一类对突触活动具有增强敏感性的新型转录传感器。
