The Epitranscriptome and Innate Immunity.
The Epitranscriptome and Innate Immunity.
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DOI：
10.1371/journal.pgen.1005687
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发表时间：
2015-12
期刊：
影响因子：
4.5
通讯作者：
Keegan LP
中科院分区：
文献类型：
--
作者：
O'Connell MA;Mannion NM;Keegan LP
我们对RNA碱基修饰的多样性和丰度的了解正在迅速增加。修饰碱基在trna、rnas、翻译、剪接、RNA干扰和其他RNA过程中起着至关重要的作用，现在越来越多地在所有类型的转录本中被检测到。与这种RNA修饰的多样性，特别是mrna和长链非编码RNA相关的新的生物学原理能否被确定？这篇综述将主要通过关注腺嘌呤脱氨酶作用于RNA （ADAR）酶的腺苷到肌苷（a -to- i） RNA编辑来探讨这个问题，该酶在过去20年中已经被广泛研究并具有广泛的作用。在人类转录组中已经鉴定出超过1亿个腺苷到肌苷的编辑位点，大多数位于嵌入的Alu序列中，这些序列在转录本中形成潜在的先天免疫刺激dsRNA发夹。最近的研究表明，表转录组中的肌苷和ADAR1蛋白对内源性序列形成的宿主dsRNA建立了先天免疫耐受。检测病毒核酸的先天免疫传感器是外转录组RNA修饰的读者之一，尽管这确实排除了广泛的其他修饰作用。
Our knowledge of the variety and abundances of RNA base modifications is rapidly increasing. Modified bases have critical roles in tRNAs, rRNAs, translation, splicing, RNA interference, and other RNA processes, and are now increasingly detected in all types of transcripts. Can new biological principles associated with this diversity of RNA modifications, particularly in mRNAs and long non-coding RNAs, be identified? This review will explore this question by focusing primarily on adenosine to inosine (A-to-I) RNA editing by the adenine deaminase acting on RNA (ADAR) enzymes that have been intensively studied for the past 20 years and have a wide range of effects. Over 100 million adenosine to inosine editing sites have been identified in the human transcriptome, mostly in embedded Alu sequences that form potentially innate immune-stimulating dsRNA hairpins in transcripts. Recent research has demonstrated that inosine in the epitranscriptome and ADAR1 protein establish innate immune tolerance for host dsRNA formed by endogenous sequences. Innate immune sensors that detect viral nucleic acids are among the readers of epitranscriptome RNA modifications, though this does preclude a wide range of other modification effects.