Investigation into the role of mRNA capping enzyme CMTR1 in liver tumorigenesis

CMTR 1是一种甲基转移酶，负责完成mRNA的Cap-1结构，使先天免疫系统能够区分自身和非自身RNA转录物，并在翻译的同时帮助RNA加工。RNA加帽酶的最新研究表明，这些酶通过调节组蛋白和核糖体生物合成在T细胞活化和ESC分化中发挥作用。未发表的数据指出CMTR 1在肝脏中的独特作用，在小鼠模型中，这种酶的缺乏会诱导纤维化并加速肿瘤发生。为了在WT和肿瘤肝细胞中检测CMTR 1，将使用来自WT和致癌小鼠模型的肝脏样本。将通过多种技术的组合进行表征，包括：蛋白质印迹法、凝胶过滤色谱法、免疫沉淀法和质谱法。在生成适当模型后，将通过RNA和ChIP seq和基于细胞的测定法确定CMTR 1表征和结合伴侣的生物学相关性。

CMTR1 is a methyltransferase responsible for completion of the Cap-1 structure of mRNA, which permits the innate immune system to differentiate self from non-self RNA transcripts and aids RNA processing alongside translation. Recent studies in RNA-capping enzymes suggest a role for these enzymes in T-cell activation and ESC differentiation via regulation of histone and ribosome biogenesis. Unpublished data points to a unique role for CMTR1 in the liver, where the absence of this enzyme induces fibrosis and hastens tumorigenesis in mouse models. To characterise CMTR1 in WT and tumour liver cells, liver samples from WT and oncogenic mouse models will be used. Characterisation will be enabled via a combination of techniques including: Western blotting, gel filtration chromatography, immunoprecipitation, and mass spectrometry. Biological relevance of CMTR1 characterisation and binding partners will be determined by RNA and ChIP seq and cell-based assays upon generation of the appropriate models.