Li Lian-Ju, Fan Yin-Guang, Leng Rui-Xue, Pan Hai-Feng, Ye Dong-Qing
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Hefei 230032, Anhui, China.
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Hefei 230032, Anhui, China.
Mol Immunol. 2018 Jan;93:55-63. doi: 10.1016/j.molimm.2017.11.009. Epub 2017 Nov 13.
The field of mA modification and epitranscriptomics has recently attracted much attention. More methods allowing for precise mA site profiling and location are developed and crucial players of mA modification machinery are increasingly identified. Although some challenges remain, mA modification is found to modulate almost all aspects of RNA metabolism, such as splicing, stability, structure, translation, and export. Thus, mA modification adds a new layer of post-transcriptional gene expression regulation, and it is implicated in T cell response to HIV infection, type I interferon production, and T cell differentiation and homeostasis. Moreover, evidence supporting its involvement in various human diseases including cancers is accumulating. Given the role of mA modification in gene expression regulation and immune response, it invites the speculation that mA modification may justify the pathogenesis of systemic lupus erythematosus (SLE) and take part in the initiation and progression of SLE. In this review, we introduce the widespread existence of mA modification and briefly discuss components of mA modification machinery in mammals. We mainly summarize the studies reporting the mechanisms of mA modification in gene expression regulation through modulating pre-mRNA splicing, mRNA stability, RNA structure, translation, and pri-miRNA processing. Biological functions related to immune response of mA modification and the implication of mA modification in cancers are highlighted. In the end, we surmise the potential link between mA modification and SLE.
N⁶-甲基腺嘌呤（mA）修饰和表观转录组学领域最近备受关注。越来越多能够实现精确的mA位点分析和定位的方法被开发出来，并且mA修饰机制的关键参与者也日益被识别。尽管仍存在一些挑战，但人们发现mA修饰几乎能调控RNA代谢的各个方面，如剪接、稳定性、结构、翻译和输出。因此，mA修饰为转录后基因表达调控增添了新的层面，并且与T细胞对HIV感染的反应、I型干扰素的产生以及T细胞分化和稳态有关。此外，支持其参与包括癌症在内的各种人类疾病的证据也在不断积累。鉴于mA修饰在基因表达调控和免疫反应中的作用，有人推测mA修饰可能是系统性红斑狼疮（SLE）发病机制的原因，并参与SLE的起始和进展。在这篇综述中，我们介绍了mA修饰的广泛存在，并简要讨论了哺乳动物中mA修饰机制的组成部分。我们主要总结了通过调节前体mRNA剪接、mRNA稳定性、RNA结构、翻译和初级微小RNA（pri-miRNA）加工来报道mA修饰在基因表达调控中的机制的研究。突出了与mA修饰免疫反应相关的生物学功能以及mA修饰在癌症中的意义。最后，我们推测了mA修饰与SLE之间的潜在联系。
