Discovery of m(7)G-cap in eukaryotic mRNAs.

Discovery of m(7)G-cap in eukaryotic mRNAs.
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DOI:
10.2183/pjab.91.394
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发表时间:
2015
期刊:
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子:
--
通讯作者:
Furuichi Y
Furuichi Y
中科院分区:
其他
文献类型:
--
作者:
Furuichi Y

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20世纪70年代初,日本国立遗传学研究所对昆虫细胞质多角体病毒(CPV)基因组RNA的末端结构进行了分析,在双链RNA基因组的5 '端发现了一个2'-O-甲基化的核苷酸。这一发现促使我将S-腺苷-L-甲硫氨酸(一种天然的甲基化供体)加入到含有RNA聚合酶的病毒的体外转录反应中。这一努力导致了前所未有的mRNA合成,在家蚕CPV和人呼肠孤病毒和牛痘病毒的转录中产生了独特的封闭和甲基化的5′端结构(后来称为“cap”或“m7 G-cap”),这些病毒颗粒中含有RNA聚合酶。对病毒的初步研究为发现通常存在于真核生物细胞mRNA中的5′-cap m7 GpppNm结构铺平了道路。我参与了这些研究,并能够解释帽合成的途径和5′帽(和帽)在基因表达过程中的意义,包括转录和蛋白质合成。在这篇综述文章中,我集中在这些最初的研究,最终导致我们的mRNA加帽的新范例的描述。
Terminal structure analysis of an insect cytoplasmic polyhedrosis virus (CPV) genome RNA in the early 1970s at the National Institute of Genetics in Japan yielded a 2′-O-methylated nucleotide in the 5′ end of double-stranded RNA genome. This finding prompted me to add S-adenosyl-L-methionine, a natural methylation donor, to the in vitro transcription reaction of viruses that contain RNA polymerase. This effort resulted in unprecedented mRNA synthesis that generates a unique blocked and methylated 5′ terminal structure (referred later to as “cap” or “m7G-cap”) in the transcription of silkworm CPV and human reovirus and vaccinia viruses that contain RNA polymerase in virus particles. Initial studies with viruses paved the way to discover the 5′-cap m7GpppNm structure present generally in cellular mRNAs of eukaryotes. I participated in those studies and was able to explain the pathway of cap synthesis and the significance of the 5′ cap (and capping) in gene expression processes, including transcription and protein synthesis. In this review article I concentrate on the description of these initial studies that eventually led us to a new paradigm of mRNA capping.