Sheffield Institute For Nucleic Acids (SInFoNiA), Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court Western Bank, Sheffield, S10 2TN, UK.
Sci Rep. 2018 Sep 14;8(1):13827. doi: 10.1038/s41598-018-32310-8.
N-methyladenosine (mA) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Recruitment of the TREX mRNA export complex to mRNA is driven by transcription, 5' capping and pre-mRNA splicing. Here we identify a fourth mechanism in human cells driving the association of TREX with mRNA involving the mA methylase complex. We show that the mA complex recruits TREX to mA modified mRNAs and this process is essential for their efficient export. TREX also stimulates recruitment of the mA reader protein YTHDC1 to the mRNA and the mA complex influences the interaction of TREX with YTHDC1. Together our studies reveal a key role for TREX in the export of mA modified mRNAs.
N6-甲基腺苷（m6A）是真核 mRNA 中最丰富的内部修饰物。 此前的研究表明，这种修饰会改变 mRNA 的输出动力学，但其分子细节仍知之甚少。TREX mRNA 输出复合物与 mRNA 的募集是由转录、5' 加帽和前体 mRNA 剪接驱动的。在这里，我们在人类细胞中鉴定出了第四个涉及 m6A 甲基转移酶复合物的机制，该机制可驱动 TREX 与 mRNA 的结合。我们发现 m6A 复合物将 TREX 募集到 m6A 修饰的 mRNA 上，该过程对于它们的有效输出是必需的。TREX 还可刺激 m6A 读蛋白 YTHDC1 与 mRNA 的募集，并且 m6A 复合物会影响 TREX 与 YTHDC1 的相互作用。总的来说，我们的研究揭示了 TREX 在 m6A 修饰的 mRNA 输出中的关键作用。
