Transcription initiation by RNA polymerase II is inhibited by S-adenosylhomocysteine.
Transcription initiation by RNA polymerase II is inhibited by S-adenosylhomocysteine.
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DOI：
10.1073/pnas.79.19.5842
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发表时间：
1982-10
影响因子：
11.1
通讯作者：
R. Jove;J. Manley
中科院分区：
文献类型：
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作者：
R. Jove;J. Manley
大多数真核生物mRNA在其5'末端通过鸟苷酰化和甲基化被封闭。这些“帽结构”已被证明在增加mRNA的稳定性和可翻译性方面发挥重要作用。先前的体外和体内数据表明，这些修改发生在RNA聚合酶II合成RNA转录本的极早期。在这里，我们表明，S-腺苷高半胱氨酸（HCY），产品和抑制剂的甲基转移反应，抑制转录起始的RNA聚合酶II，但不是RNA聚合酶III，在HeLa全细胞裂解液。在起始过程中必须存在Hcy以抑制转录，并且不影响RNA聚合酶II的延伸或所得转录物的稳定性。此外，HCY不抑制纯化的HeLa RNA聚合酶II的转录。这些结果表明，5 '-帽结构的形成与转录的起始相关联，并且与起始时加帽酶和RNA聚合酶II之间的密切关联一致。
Most eukaryotic mRNAs are blocked at their 5' termini by guanylylation and methylation. These "cap structures" have been shown to play important roles in increasing the stability and translatability of mRNAs. Previous in vitro and in vivo data suggest that these modifications occur extremely early in the synthesis of RNA transcripts by RNA polymerase II. Here we show that S-adenosylhomocysteine (AdoHcy), both a product and an inhibitor of transmethylation reactions, inhibits transcription initiation by RNA polymerase II, but not by RNA polymerase III, in a HeLa whole-cell lysate. AdoHcy must be present during initiation to inhibit transcription and does not affect elongation by RNA polymerase II or the stability of the resultant transcript. Furthermore, AdoHcy does not inhibit transcription by purified HeLa RNA polymerase II. These results suggest that formation of the 5'-cap structure is coupled to initiation of transcription and is consistent with a close association between the capping enzymes and RNA polymerase II at the time of initiation.