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特异性敲低海马RNA甲基转移酶Pcif1对空间学习记忆的影响与机制研究
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作者 孙祖浩 所信君 +3 位作者 夏贤友 赵爽 窦妍 于春水 《天津医药》 CAS 北大核心 2022年第8期802-809,共8页
目的探索RNA甲基转移酶Pcif1对海马相关空间学习记忆的影响及分子机制。方法选择27只8周龄的雄性C57BL/6J Nifdc小鼠进行动物实验,随机分为3组(每组9只):Pcif1敲低组(对小鼠海马立体定位注射1μL的腺相关病毒包装的靶向Pcif1的shRNA)、... 目的探索RNA甲基转移酶Pcif1对海马相关空间学习记忆的影响及分子机制。方法选择27只8周龄的雄性C57BL/6J Nifdc小鼠进行动物实验,随机分为3组(每组9只):Pcif1敲低组(对小鼠海马立体定位注射1μL的腺相关病毒包装的靶向Pcif1的shRNA)、假手术组(对小鼠海马立体定位注射1μL的对照腺相关病毒)、野生组(不做处理)。3周后,Morris水迷宫实验用于测试小鼠的空间学习记忆能力,Western blot检测小鼠海马组织中相关蛋白的表达。选择小鼠海马神经元来源的HT22细胞系进行体外实验,细胞分为2组:HT22-shPcif1组(通过慢病毒包装的靶向Pcif1的shRNA实现细胞Pcif1的敲低)和HT22-Ctrl组(通过对照慢病毒感染细胞),通过全转录组测序(RNA-seq)、细胞毒性实验(CCK-8)、细胞划痕和流式细胞术研究敲低Pcif1影响学习记忆的机制。结果与野生组和假手术组相比,敲低组小鼠的空间学习记忆能力增强,小鼠海马中的抗凋亡蛋白Bcl-2表达上调。与HT22-Ctrl组相比,HT22-shPcif1组差异表达的基因富集到凋亡、迁移和增殖通路,细胞迁移能力增强,在400μmol/L H_(2)O_(2)条件下细胞增殖能力提高,凋亡水平下降。结论选择性敲低海马Pcif1可以促进小鼠的空间学习记忆,其机制可能与抗凋亡蛋白上调,促进细胞迁移和增殖有关。 展开更多
关键词 tRNA甲基转移酶类 海马 空间学习 空间记忆 细胞凋亡 细胞增殖 pcif1
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Cap-specific terminal N6-methyladeonsine methylation of RNA mediated by PCIF1 and possible therapeutic implications
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作者 Hui Zeng Yidong Wu Xinghua Long 《Genes & Diseases》 2025年第1期172-181,共10页
Posttranscriptional RNA modification is an important mode of epigenetic regulation in various biological and pathological contexts.N6,2′-O-dimethyladenosine(m6Am)is one of the most abundant methylation modifications ... Posttranscriptional RNA modification is an important mode of epigenetic regulation in various biological and pathological contexts.N6,2′-O-dimethyladenosine(m6Am)is one of the most abundant methylation modifications in mammals and usually occurs at the first transcribed nucleotide.Accumulating evidence indicates that m6Am modifications have important roles in RNA metabolism and physiological and pathological processes.PCIF1(phosphorylated C-terminal domain interacting factor 1)is a protein that can bind to the phosphorylated C-terminal domain of RNA polymeraseⅡthrough its WW domain.PCIF1 is named after this binding ability.Recently,PCIF1 has been identified as a cap-specific adenine N6-methyltransferase responsible for m6Am formation.Discovered as the sole m6Am methyltransferase for mammalian mRNA,PCIF1 has since received more extensive and in-depth study.Dysregulation of PCIF1 contributes to various pathological processes.Targeting PCIF1 may hold promising therapeutic significance.In this review,we provide an overview of the current knowledge of PCIF1.We explore the current understanding of the structure and the biological characteristics of PCIF1.We further review the molecular mechanisms of PCIF1 in cancer and viral infection and discuss its therapeutic potential. 展开更多
关键词 Cancer m^(6)Am pcif1 RNA modification Virus infection
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