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Retroelement-derived RNA and its role in the brain
Seminars in Cell & Developmental Biology ( IF 6.2 ) Pub Date : 2020-11-21 , DOI: 10.1016/j.semcdb.2020.11.001
Taylor A Evans 1 , Jennifer Ann Erwin 2
Affiliation  

Comprising ~40% of the human genome, retroelements are mobile genetic elements which are transcribed into RNA, then reverse-transcribed into DNA and inserted into a new site in the genome. Retroelements are referred to as “genetic parasites”, residing among host genes and relying on host machinery for transcription and evolutionary propagation. The healthy brain has the highest expression of retroelement-derived sequences compared to other somatic tissue, which leads to the question: how does retroelement-derived RNA influence human traits and cellular states? While the functional importance of upregulating retroelement expression in the brain is an active area of research, RNA species derived from retroelements influence both self- and host gene expression by contributing to chromatin remodeling, alternative splicing, somatic mosaicism and translational repression. Here, we review the emerging evidence that the functional importance of RNA derived from retroelements is multifaceted. Retroelements can influence organismal states through the seeding of epigenetic states in chromatin, the production of structured RNA and even catalytically active ribozymes, the generation of cytoplasmic ssDNA and RNA/DNA hybrids, the production of viral-like proteins, and the generation of somatic mutations. Comparative sequencing suggests that retroelements can contribute to intraspecies variation through these mechanisms to alter transcript identity and abundance. In humans, an increasing number of neurodevelopmental and neurodegenerative conditions are associated with dysregulated retroelements, including Aicardi-Goutieres syndrome (AGS), Rett syndrome (RTT), Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease (AD), multiple sclerosis (MS), schizophrenia (SZ), and aging. Taken together, these concepts suggest a larger functional role for RNA derived from retroelements. This review aims to define retroelement-derived RNA, discuss how it impacts the mammalian genome, as well as summarize data supporting phenotypic consequences of this unique RNA subset in the brain.



中文翻译:

逆转录元素衍生的 RNA 及其在大脑中的作用

逆转录元件占人类基因组的约 40%,是可移动的遗传元件,它们被转录成 RNA,然后逆转录成 DNA 并插入基因组中的新位点。逆转录元件被称为“遗传寄生虫”,存在于宿主基因中,依赖宿主机器进行转录和进化繁殖。与其他体细胞组织相比,健康的大脑具有最高的逆转录衍生序列表达,这就引出了一个问题:逆转录衍生的 RNA 如何影响人类特征和细胞状态?虽然上调大脑中逆转录元件表达的功能重要性是一个活跃的研究领域,但源自逆转录元件的 RNA 种类通过促进染色质重塑、选择性剪接、体细胞嵌合和翻译抑制。在这里,我们回顾了新出现的证据,这些证据表明源自逆转录元件的 RNA 的功能重要性是多方面的。逆转录元件可以通过在染色质中播种表观遗传状态、结构化 RNA 甚至催化活性核酶的产生、细胞质 ssDNA 和 RNA/DNA 杂合体的产生、病毒样蛋白的产生以及体细胞突变的产生来影响有机体状态. 比较测序表明,逆转录元件可以通过这些机制导致种内变异,从而改变转录本的身份和丰度。在人类中,越来越多的神经发育和神经退行性疾病与失调的逆转录因子有关,包括 Aicardi-Goutieres 综合征 (AGS)、Rett 综合征 (RTT)、肌萎缩侧索硬化症 (ALS)、阿尔茨海默病 (AD)、多发性硬化症 (MS)、精神分裂症 (SZ) 和衰老。总之,这些概念表明源自逆转录元件的 RNA 具有更大的功能作用。这篇综述旨在定义逆转录元素衍生的 RNA,讨论它如何影响哺乳动物基因组,并总结支持大脑中这种独特 RNA 子集的表型后果的数据。

更新日期:2020-11-21
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