Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
School of Integrative Plant Science, Cornell University, Ithaca, NY 14853, USA.
Dev Cell. 2021 Jan 11;56(1):125-140.e6. doi: 10.1016/j.devcel.2020.11.009. Epub 2020 Dec 7.
Although eukaryotic messenger RNAs (mRNAs) normally possess a 5' end N-methyl guanosine (mG) cap, a non-canonical 5' nicotinamide adenine dinucleotide (NAD) cap can tag certain transcripts for degradation mediated by the NAD decapping enzyme DXO1. Despite this importance, whether NAD capping dynamically responds to specific stimuli to regulate eukaryotic transcriptomes remains unknown. Here, we reveal a link between NAD capping and tissue- and hormone response-specific mRNA stability. In the absence of DXO1 function, transcripts displaying a high proportion of NAD capping are instead processed into RNA-dependent RNA polymerase 6-dependent small RNAs, resulting in their continued turnover likely to free the NAD molecules. Additionally, the NAD-capped transcriptome is significantly remodeled in response to the essential plant hormone abscisic acid in a mechanism that is primarily independent of DXO1. Overall, our findings reveal a previously uncharacterized and essential role of NAD capping in dynamically regulating transcript stability during specific physiological responses.
虽然真核信使 RNA（mRNA）通常具有 5'端 N-甲基鸟苷（mG）帽，但非典型的 5'烟酰胺腺嘌呤二核苷酸（NAD）帽可以标记某些转录本，使其通过 NAD 脱帽酶 DXO1 介导降解。尽管这很重要，但 NAD 加帽是否能动态响应特定刺激来调节真核转录组仍然未知。在这里，我们揭示了 NAD 加帽与组织和激素反应特异性 mRNA 稳定性之间的联系。在缺乏 DXO1 功能的情况下，显示出高比例 NAD 加帽的转录本被加工成 RNA 依赖性 RNA 聚合酶 6 依赖性小 RNA，导致其持续周转，可能释放 NAD 分子。此外，在一种主要不依赖于 DXO1 的机制中，NAD 加帽的转录组会对必需的植物激素脱落酸做出显著的重塑反应。总的来说，我们的发现揭示了 NAD 加帽在特定生理反应中动态调节转录本稳定性方面的一个以前未被描述的基本作用。
