TRMO,也称为tRNA (adenine37-N6)-methyltransferase TrmO,是一种重要的RNA N6-甲基腺苷(m6A)甲基转移酶。m6A是一种普遍存在于真核细胞RNA上的表观遗传修饰,参与调控RNA的稳定性和功能,影响基因表达和生物学过程。TRMO与另一个蛋白质Mettl3形成复合物,共同催化m6A的生成。m6A修饰在许多生物学过程中发挥作用,包括细胞分化、发育、代谢和疾病发生[1]。
TRMO在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病心肌病、结直肠癌和Wilms瘤。在动脉粥样硬化中,TRMO通过NF-κB/IL-6信号通路介导巨噬细胞的炎症反应,促进动脉粥样硬化斑块的形成[2]。在糖尿病心肌病中,TRMO通过下调lncRNA TINCR抑制焦亡和糖尿病心肌病的发生[3]。在结直肠癌中,TRMO通过m6A修饰抑制SOX4 mRNA的表达,从而抑制肿瘤的转移[4]。此外,TRMO的基因多态性与中国儿童Wilms瘤的易感性降低相关[5]。
高风险神经母细胞瘤(NB)患者中,TRMO表达显著上调,与不良预后有强相关性。TRMO通过m6A-YTHDF1依赖机制抑制YWHAH表达,激活PI3K/AKT信号通路,促进NB细胞活性[6]。TRMO通过促进PRC2和KDM5B在二价结构域上的结合,影响组蛋白修饰,进而调控二价结构基因的表达[7]
TRMO不仅在RNA修饰中发挥作用,还具有独立的染色质调控功能。TRMO可以与H3K27me3结合,招募KDM6B诱导H3K27me3的去甲基化,从而影响基因表达和干细胞的多能性维持[8]。此外,TRMO还可以通过下调lncRNA XIST的表达抑制结直肠癌的增殖和转移[9]。
综上所述,TRMO是一种重要的RNA甲基转移酶,参与调控RNA的稳定性和功能,影响基因表达和生物学过程。TRMO在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病心肌病、结直肠癌和Wilms瘤。此外,TRMO还具有独立的染色质调控功能,影响基因表达和干细胞的多能性维持。TRMO的研究有助于深入理解RNA表观遗传修饰的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
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2. Shimada, Miho, Chen, Wei-Yi, Nakadai, Tomoyoshi, Rhodes, Daniela, Roeder, Robert G. 2019. Gene-Specific H1 Eviction through a Transcriptional Activator→p300→NAP1→H1 Pathway. In Molecular cell, 74, 268-283.e5. doi:10.1016/j.molcel.2019.02.016. https://pubmed.ncbi.nlm.nih.gov/30902546/
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