在各种表观转录组学修饰中，除了m6A在mRNA和lncRNA中作为最重要的修饰类型而被广泛研究外，其他修饰如m1A、m5C、ac4C、m7G和Ψ，也越来越多地被发现具有新的生物学功能或临床价值。康成生物|数谱生物现在提供Arraystar表观转录组芯片和表观转录组测序服务，在全转录组范围内助力分析这些修饰的关键作用。
m1A
m1A（1-甲基腺嘌呤）是一种新发现的mRNA和lncRNA修饰[1-3]。该修饰可以通过其对Watson-Crick碱基配对的破坏，影响RNA的二级结构和蛋白质-RNA相互作用[1, 2]。在互作蛋白层面上，目前已知一小部分mRNA上的m1A是由TRM6–TRM61复合物介导添加的[1, 3]；YTHDF2是一种可能的m1A读取蛋白，它可以降低带有m1A修饰的RNA的稳定性；YTHDF3也可以结合某些m1A甲基化的转录本，特别是IGF1R（胰岛素样生长因子1受体），从而抑制滋养层细胞的侵袭；ALKBH3是目前唯一已知的能够去除mRNA上m1A的蛋白；m1A调节失常与许多疾病有关。例如， CSF1 (集落刺激因子1) mRNA的m1A去除促进其mRNA的稳定性，，而ALKBH3可以通过去除Aurora A mRNA上的m1A抑制纤毛形成。在胃肠道癌中，ErbB2、mTOR和AKT1S1基因也是通过m1A修饰水平的变化调节ErbB和mTOR通路的[8]。此外，m1A在应激诱导的颗粒化过程中也有保护作用[9]。
m5C
虽然在丰富的非编码小RNAs中已经确定了m5C（5-甲基胞嘧啶）的存在，但它在编码性mRNA中的存在直到最近才被证实[10, 11]。NSUN2[12]和NSUN6[13, 14]是在mRNA上添加m5C修饰的writer，而TET2则作为去甲基化酶将m5C氧化为hm5C[15]。目前有两种可能的m5C reader蛋白：ALYREF，它促进m5C甲基化的mRNA的核质运输[12]，以及YBX1，它可以稳定带有m5C修饰的mRNA[16, 17]。mRNA m5C修饰具有多种重要的生物学功能，包括作为DNA损伤信号来调节DNA修复[18]、参与干细胞分化[11]、促进母系-合子转换[17]、以及通过控制细胞周期进程促进脂质生成[19]。m5C也与一些疾病相关，如膀胱癌的发病机制[16]和病原体感染诱导的髓系细胞生成[15]。
m7G
m7G（7-甲基鸟嘌呤）是真核生物mRNA 5’端帽子上的一种带正电荷的必需修饰[20]，它有助于指导mRNA的翻译、剪接、核质运输和免于降解。m7G也存在于mRNA内部[21]和miRNA中[22]，m7G修饰由哺乳动物中的METTL1-WDR4异二聚体介导添加。mRNA内部的m7G甲基化可以增加mRNA的翻译效率[21]，在CDS和3’ UTR区域有显著的积累[23]，并且在H2O2和热休克处理下动态调节修饰水平。miRNA中的m7G可以通过破坏几个pri-miRNA转录本中存在的G-四链体，破坏这种抑制性的二级结构来促进miRNA的加工。在功能上，有研究证明miRNA中的m7G修饰参与抑制肺癌细胞迁移[22]。tRNA [24-27]和18S rRNA [28]也是m7G修饰的典型底物。tRNA上的m7G修饰由Mettl1/Wdr4介导添加，是正常翻译mRNA、胚胎干细胞自我更新/分化[24]，以及癌症中增加致癌性mRNA翻译[25-27]所必需的。人类18S rRNA上位置1639处的m7G修饰与rRNA前体加工和40S核糖体亚基生物合成有关[29]。
ac4C
ac4C（N4-乙酰胞嘧啶）是一种经典的rRNA和tRNA修饰，最近也被发现存在于mRNA中[30]。4NAT10是细胞RNA中ac4C形成的唯一乙酰化酶[30]。在测序中得到的ac4C峰靠近翻译起始位点，在CDS和5’-UTR区域富集，但在3’-UTRs中没有检测到[30]。ac4C可以稳定mRNAs并促进翻译[30]，特别是在wobble位点中的ac4C修饰可以显著提高翻译效率[30]。mRNA乙酰化的生物学功能和疾病相关性很大程度上还是未知的。目前已知的有HIV-1 RNA上的ac4C积累可以增强病毒RNA的稳定性，从而促进HIV-1复制[31]。并且，也有研究发现ac4C可以通过其选择性招募PCBP2蛋白到IRES元件来增强肠道病毒71（EV71） RNA 的复制和致病性，从而增加RNA稳定性和RNA聚合酶对病毒RNA的结合[32]。
Ψ
Ψ(假尿嘧啶)是人类细胞总RNA中最丰富的修饰，它存在于大多数RNA中，包括mRNAs[33, 34]。Ψ在mRNA上主要是由PUS1[35]、PUS7[36]和TRUB1[36]等酶介导添加的，在此之外，TRUB2和RPUSD3也参与了线粒体mRNA中特定残基的假尿嘧啶修饰[37]。mRNA编码区域中的假尿嘧啶可以通过促进含有假尿嘧啶的密码子上的氨基酸替换来改变翻译产物[38]。假尿嘧啶RNA修饰是在转录过程中加入到pre-mRNA上的，这可以影响其在可变剪接区域中的富集，从而影响可变剪接过程中pre-mRNA的加工方式[39]。在最近的研究中，有研究者发现干扰素可以诱导干扰素刺激基因转录本中的假尿嘧啶修饰，暗示假尿嘧啶在IFN信号通路和抗病毒防御中的作用[40]。
Arraystar表观转录组芯片和表观转录组测序
为了分析和探索这些表观转录组修饰，康成生物|数谱生物提供了Arraystar表观转录组芯片服务和表观转录组测序服务，既可以检测mRNA，也可以检测lncRNA的修饰。我们用特异性抗体免疫沉淀total RNA选择性检测和定量特定转录本上的修饰。更多细节，请参见上面链接的网页。
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