Center for Molecular Neuroscience, Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232-8548, USA.
Neurobiol Dis. 2012 Jan;45(1):8-13. doi: 10.1016/j.nbd.2011.08.026. Epub 2011 Sep 3.
Initially identified as an RNA modification in the anticodon loop of tRNAs from animal, plant and eubacterial origin, the deamination of adenosine-to-inosine by RNA editing has become increasingly recognized as an important RNA processing event to generate diversity in both the transcriptome and proteome and is essential for modulating the activity of numerous proteins critical for nervous system function. Here, we focus on the editing of transcripts encoding the 2C-subtype of serotonin receptor (5HT(2C)) to generate multiple receptor isoforms that differ in G-protein coupling efficacy and constitutive activity. 5HT(2C) receptors have been implicated in the regulation of anxiety, components of the stress response, and are thought to play a role in compulsive behavioral disorders, depression and drug addiction. A number of studies have been conducted to assess whether 5HT(2C) editing is altered in individuals suffering from psychiatric disorders, yet the results from these studies have been inconsistent, and thus inconclusive. This review provides a discussion of the challenges involved with characterizing 5HT(2C) editing patterns in human postmortem tissue samples and how differences in quantitative methodology have contributed to the observed inconsistencies between multiple laboratories. Additionally, we discuss new high-throughput sequencing tools, which provide an opportunity to overcome previous methodological challenges, and permit reliable systematic analyses of RNA editing in control and pathologic disease states.
最初在动物、植物和真细菌来源的 tRNA 的反密码子环中被鉴定为 RNA 修饰，通过 RNA 编辑使腺苷脱氨酶转化为肌苷已越来越被认为是一种重要的 RNA 加工事件，可在转录组和蛋白质组中产生多样性，并对调节许多对神经系统功能至关重要的蛋白质的活性至关重要。在这里，我们专注于编辑编码 5-羟色胺受体（5HT（2C））2C 亚型的转录本，以生成在 G 蛋白偶联效率和组成活性方面存在差异的多种受体同工型。5HT（2C）受体被认为参与调节焦虑、应激反应的组成部分，并且被认为在强迫性行为障碍、抑郁和药物成瘾中发挥作用。已经进行了许多研究来评估患有精神疾病的个体中 5HT（2C）编辑是否改变，但这些研究的结果不一致，因此没有定论。本综述讨论了在人类死后组织样本中描述 5HT（2C）编辑模式所涉及的挑战，以及定量方法学的差异如何导致多个实验室之间观察到的不一致。此外，我们讨论了新的高通量测序工具，这些工具为克服以前的方法学挑战提供了机会，并允许对对照和病理疾病状态下的 RNA 编辑进行可靠的系统分析。
