DOI：10.1038/nature18622 作者：Bryce E. Nickels
摘要 : 为防止降解，信使RNA (mRNA)的两端都被改变以阻断核酸酶。
为防止降解，信使RNA (mRNA)的两端都被改变以阻断核酸酶。直到最近，已知保护5'端的惟一改变是一个7-甲基鸟苷酸 “帽”，尽管也已发现一些mRNA用NAD+ 或dpCoA来取而代之。人们曾假设这些另类“帽”的添加机制是相同的。然而，Bryce Nickels及同事现在发现，另类“帽”采用一个截然不同的机制，按照该机制它们是在转录启动过程中、而不是之后被添加上去的。在细菌和真核细胞中，RNA聚合酶都采用这些基团作为非经典启动核苷酸，它们的使用在功能上是有后果的。
The chemical nature of the 5′ end of RNA is a key determinant of RNA stability, processing, localization and translation efficiency1, 2, and has been proposed to provide a layer of ‘epitranscriptomic’ gene regulation3. Recently it has been shown that some bacterial RNA species carry a 5′-end structure reminiscent of the 5′ 7-methylguanylate ‘cap’ in eukaryotic RNA. In particular, RNA species containing a 5′-end nicotinamide adenine dinucleotide (NAD+) or 3′-desphospho-coenzyme A (dpCoA) have been identified in both Gram-negative and Gram-positive bacteria3, 4, 5, 6. It has been proposed that NAD+, reduced NAD+ (NADH) and dpCoA caps are added to RNA after transcription initiation, in a manner analogous to the addition of 7-methylguanylate caps6, 7, 8. Here we show instead that NAD+, NADH and dpCoA are incorporated into RNA during transcription initiation, by serving as non-canonical initiating nucleotides (NCINs) forde novo transcription initiation by cellular RNA polymerase (RNAP). We further show that both bacterial RNAP and eukaryotic RNAP II incorporate NCIN caps, that promoter DNA sequences at and upstream of the transcription start site determine the efficiency of NCIN capping, that NCIN capping occurs in vivo, and that NCIN capping has functional consequences. We report crystal structures of transcription initiation complexes containing NCIN-capped RNA products. Our results define the mechanism and structural basis of NCIN capping, and suggest that NCIN-mediated ‘ab initio capping’ may occur in all organisms.
来源： Nature 浏览次数：1