CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription.
CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription.
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DOI：
10.1016/j.molcel.2016.02.008
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发表时间：
2016-03-03
期刊：
影响因子：
16
通讯作者：
Cowling VH
中科院分区：
文献类型：
--
作者：
Aregger M;Kaskar A;Varshney D;Fernandez-Sanchez ME;Inesta-Vaquera FA;Weidlich S;Cowling VH
具有翻译能力的mRNA的产生依赖于RNA聚合酶II转录产物被添加7-甲基鸟苷(M7G)帽修饰。调节剪接、核输出和翻译启动的因子通过CAP被招募到转录本中。帽子结构由几个活性组成，并由RNMT(RNA鸟嘌呤-7甲基转移酶)完成，RNMT催化帽子鸟苷的N7甲基化。我们报道了CDK1-Cyclin B1在细胞周期的G2/M期磷酸化T77上的RNMT调节域。RNMT T77的磷酸化通过抑制与RNMT抑制剂KPNA2的相互作用而直接或间接地激活该酶。RNMT T77磷酸化导致G1期开始时m7G帽甲基转移酶活性升高，使mRNA封顶与核膜重塑后发生的转录爆发相协调。RNMT T77磷酸化是产生蛋白质队列所必需的，抑制RNMT T77磷酸化降低细胞增殖率。CDK1-Cyclin B1磷酸化RNMT在T77上的mRNA帽甲基转移酶T77磷酸化增加mRNA帽甲基转移酶活性CDK1-Cyclin B1激活RNMT协调有丝分裂后转录和封顶RNMT T77磷酸化是基因表达和细胞增殖的速率限制，mRNA的加工和翻译依赖于mRNA帽结构。Aregger等人。报道称，细胞周期调节因子CDK1-Cyclin B1磷酸化并激活mRNA帽甲基转移酶RNMT，导致有丝分裂后帽的活性增加。RNMT的磷酸化协调G1期转录和翻译启动所需的帽的形成。
The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate. CDK1-cyclin B1 phosphorylates the mRNA cap methyltransferase RNMT on T77 RNMT T77 phosphorylation increases mRNA cap methyltransferase activity CDK1-cyclin B1 activation of RNMT coordinates post-mitotic transcription and capping RNMT T77 phosphorylation is rate limiting for gene expression and cell proliferation mRNA processing and translation are dependent on the mRNA cap structure. Aregger et al. report that the cell cycle regulator CDK1-cyclin B1 phosphorylates and activates the mRNA cap methyltransferase RNMT, resulting in increased capping activity following mitosis. RNMT phosphorylation coordinates G1 phase transcription and the cap formation required for translation initiation.