强化子RNA
强化子RNA(Enhancer RNA,简称eRNA)是真核生物基因组中强化子序列转录产生的非编码RNA[1],长50nt至4000nt之间,此类RNA于2010年由RNA测序与ChIP-seq等大规模测序技术测得[2]。强化子为基因组中与RNA聚合酶Ⅱ、中介体和转录因子结合以启动基因转录的重要序列,其转录生成的强化子RNA大多留在细胞核中,此类RNA大多不稳定,易被细胞核中的外切体降解,但可能可调控其他基因的转录[3]。并非所有强化子皆可转录,有研究显示仅有少数强化子可转录产生出eRNA[4],可能为较为活跃的强化子[5]。有些强化子RNA具复杂的次级结构,并带有m6A等碱基修饰[5]。
强化子RNA可分为1D eRNA与2D eRNA两大类,两者长度、多腺苷酸化情况与转录方向皆有差异[6],1D eRNA的转录为单向,长度可达数千nt,较常被多腺苷酸化[5],一般由H3K4me1/H3K4me3比值较低的强化子转录[7];2D eRNA的转录则为双向,且长度较短,介于50nt至2000nt之间,转录的强化子H3K4me1/H3K4me3较高[8]。
有研究认为强化子RNA仅是基因转录的中的噪声,即由染色体结构疏松的区域所随机转录产生、不具重要功能的RNA[4][9][10],但有许多研究认为强化子RNA可能具重要的转录调控功能,可影响特定基因的表现,其详细机制尚不明朗,但目前已有数个假说被提出[6],有些强化子RNA可能可和组蛋白修饰酶或转录因子等调控蛋白结合,以促进该强化子所控制基因的转录,例如周期蛋白D1基因强化子转录出的eRNA可结合组蛋白乙酰转移酶以促进周期蛋白D1的转录[3],受p53调控的各目标基因之强化子p53BER也可转录出eRNA以促进各目标基因转录[11];还有些强化子RNA可能可调控其他较远位点的基因的转录[12]。有eRNA可能可作为一些癌症病理状况的生物标记[5][13]。
参考文献
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