Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Mol Cell. 2011 Nov 18;44(4):585-96. doi: 10.1016/j.molcel.2011.08.041.
The 7-methylguanosine cap added to the 5' end of mRNA is required for efficient gene expression in eukaryotes. In mammals, methylation of the guanosine cap is catalyzed by RNMT (RNA guanine-7 methyltransferase), an enzyme previously thought to function as a monomer. We have identified an obligate component of the mammalian cap methyltransferase, RAM (RNMT-Activating Mini protein)/Fam103a1, a previously uncharacterized protein. RAM consists of an N-terminal RNMT-activating domain and a C-terminal RNA-binding domain. As monomers RNMT and RAM have a relatively weak affinity for RNA; however, together their RNA affinity is significantly increased. RAM is required for efficient cap methylation in vitro and in vivo, and is indirectly required to maintain mRNA expression levels, for mRNA translation and for cell viability. Our findings demonstrate that RAM is an essential component of the core gene expression machinery.
真核生物中，mRNA 5' 端的 7-甲基鸟苷帽对于基因的高效表达是必需的。在哺乳动物中，鸟苷帽的甲基化由 RNMT（RNA 鸟嘌呤-7 甲基转移酶）催化，该酶先前被认为是单体发挥作用。我们鉴定出了一种哺乳动物帽甲基转移酶的必需成分，即 RAM（RNMT 激活小蛋白）/Fam103a1，这是一种以前未被表征的蛋白质。RAM 由一个 N 端的 RNMT 激活结构域和一个 C 端的 RNA 结合结构域组成。作为单体，RNMT 和 RAM 对 RNA 的亲和力相对较弱；但是，它们一起的 RNA 亲和力显著增加。RAM 在体外和体内都需要有效地进行帽甲基化，并且间接地需要维持 mRNA 表达水平、mRNA 翻译和细胞活力。我们的研究结果表明，RAM 是核心基因表达机器的必需组成部分。
