Human cap methyltransferase (RNMT) N-terminal non-catalytic domain mediates recruitment to transcription initiation sites
Human cap methyltransferase (RNMT) N-terminal non-catalytic domain mediates recruitment to transcription initiation sites
复制标题
DOI：
10.1042/bj20130378
复制
发表时间：
2013-10-01
影响因子：
4.1
通讯作者：
Cowling, Victoria H.
中科院分区：
文献类型：
--
作者：
Aregger, Michael;Cowling, Victoria H.
真核生物中的基因表达依赖于mRNA甲基帽，其介导mRNA加工和翻译起始。甲基帽的合成起始于向RNA pol II（聚合酶II）转录物的起始核苷酸添加7-甲基鸟苷，这主要发生在转录期间，并且在哺乳动物中由RNGTT（RNA鸟苷酰转移酶和5'磷酸酶）和RNMT（RNA鸟嘌呤-7甲基转移酶）催化。RNMT具有甲基转移酶结构域和N-末端结构域，其功能尚不清楚;它在哺乳动物中是保守的，但不是cap甲基转移酶活性所必需的。在本研究中，我们报告说，N-末端结构域是必要的和足够的RNMT招聘到转录起始位点，招聘发生在DRB（5，6-二氯-1-β-D-呋喃核糖基苯并咪唑）依赖的方式。RNMT激活亚基RAM（RNMT激活微蛋白）也通过与RNMT的相互作用被募集到转录起始位点。RNMT N端结构域是转录本表达、翻译和细胞增殖所必需的。
Gene expression in eukaryotes is dependent on the mRNA methyl cap which mediates mRNA processing and translation initiation. Synthesis of the methyl cap initiates with the addition of 7-methylguanosine to the initiating nucleotide of RNA pol II (polymerase II) transcripts, which occurs predominantly during transcription and in mammals is catalysed by RNGTT (RNA guanylyltransferase and 5' phosphatase) and RNMT (RNA guanine-7 methyltransferase). RNMT has a methyltransferase domain and an N-terminal domain whose function is unclear; it is conserved in mammals, but not required for cap methyltransferase activity. In the present study we report that the N-terminal domain is necessary and sufficient for RNMT recruitment to transcription initiation sites and that recruitment occurs in a DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole)-dependent manner. The RNMT-activating subunit, RAM (RNMT-activating miniprotein), is also recruited to transcription initiation sites via an interaction with RNMT. The RNMT N-terminal domain is required for transcript expression, translation and cell proliferation.