Nibuya Masashi, Suda Shiro, Nomura Soicihiro
Department of Neuropsychiatry, National Defense Medical College, 3-2, Namiki, Tokorozawa, 359-8531 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2003 Apr;23(2):97-104.
Two different mechanisms have been well known to regulate the amounts of various transcripts in response to internal and external environmental stimuli. First, by binding of activated transcription factors to DNA regulatory regions including the cAMP response element, hormone response element, and activator protein-1 region upstream in various genes, the rate of transcription from DNA to mRNA is regulated. Secondly, the degradation of some mRNAs related to immune responses has been reported to be regulated by binding of RNA-binding proteins to adenylate uridylate-rich elements (AU-rich elements, AREs) located in the 3'-untranslated region (3'-UTR). The original study identifying the existence of a common regulatory nucleotide sequence in the 3'-UTR of inflammatory mediator transcripts pointed out that the AREs are characteristic of immune-related functional proteins. The number of transcripts containing AREs in the 3'-UTR has increased and several neuronal proteins including beta 2-adrenergic receptor, nerve growth factor, tyrosine hydroxylase, and nitric-oxide synthase II, have been reported to have AREs. We here reviewed the recent advances in the neuropsychopharmacological understanding of post-transcriptional regulation by RNA-binding protein and also pointed out the importance of this regulation in future studies using various stress paradigms.
已知有两种不同的机制可调节各种转录本的数量,以响应内部和外部环境刺激。首先,通过激活的转录因子与包括环磷酸腺苷反应元件、激素反应元件和各种基因上游的激活蛋白-1区域在内的DNA调控区域结合,可调节从DNA到mRNA的转录速率。其次,据报道,一些与免疫反应相关的mRNA的降解是由RNA结合蛋白与位于3'非翻译区(3'-UTR)的富含腺苷酸尿苷酸元件(富含AU元件,AREs)结合来调节的。最初鉴定炎症介质转录本3'-UTR中存在共同调控核苷酸序列的研究指出,AREs是免疫相关功能蛋白的特征。3'-UTR中含有AREs的转录本数量有所增加,并且据报道,包括β2-肾上腺素能受体、神经生长因子、酪氨酸羟化酶和一氧化氮合酶II在内的几种神经元蛋白都含有AREs。我们在此回顾了RNA结合蛋白在转录后调控的神经精神药理学理解方面的最新进展,并指出了这种调控在未来使用各种应激范式的研究中的重要性。