Department of Pediatrics/Rady Children's Hospital San Diego, University of California San Diego, La Jolla, California 92093, USA.
Annu Rev Cell Dev Biol. 2012;28:555-73. doi: 10.1146/annurev-cellbio-101011-155822.
Long interspersed element-1 (LINE-1 or L1) is a repetitive DNA retrotransposon capable of duplication by a copy-and-paste genetic mechanism. Scattered throughout mammalian genomes, L1 is typically quiescent in most somatic cell types. In developing neurons, however, L1 can express and retrotranspose at high frequency. The L1 element can insert into various genomic locations including intragenic regions. These insertions can alter the dynamic of the neuronal transcriptome by changing the expression pattern of several nearby genes. The consequences of L1 genomic alterations in somatic cells are still under investigation, but the high level of mutagenesis within neurons suggests that each neuron is genetically unique. Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects. In this review, we survey the literature related to neurodevelopmental retrotransposition and discuss possible relevance to neuronal function, evolution, and neurological disease.
长散布元件-1(LINE-1 或 L1)是一种能够通过复制粘贴遗传机制进行复制的重复 DNA 反转录转座子。L1 散布在哺乳动物基因组中,在大多数体细胞类型中通常处于静止状态。然而,在发育中的神经元中,L1 可以高频表达和反转录。L1 元件可以插入各种基因组位置,包括基因内区域。这些插入可以通过改变几个附近基因的表达模式来改变神经元转录组的动态。L1 基因组改变在体细胞中的后果仍在研究中,但神经元内的高突变率表明每个神经元都是遗传独特的。此外,一些神经疾病,如雷特综合征和共济失调毛细血管扩张症,调节 L1 反转录转座的异常,这可能有助于一些病理方面。在这篇综述中,我们调查了与神经发育反转录转座相关的文献,并讨论了其与神经元功能、进化和神经疾病的可能相关性。