The DNA damage response is mediated by both DNA repair proteins and epigenetic markers. Here, we observe that N6-methyladenosine (m6A), a mark of the epitranscriptome, was common in RNAs accumulated at UV-damaged chromatin; however, inhibitors of RNA polymerases I and II did not affect the m6A RNA level at the irradiated genomic regions. After genome injury, m6A RNAs either diffused to the damaged chromatin or appeared at the lesions enzymatically. DNA damage did not change the levels of METTL3 and METTL14 methyltransferases. In a subset of irradiated cells, only the METTL16 enzyme, responsible for m6A in non-coding RNAs as well as for splicing regulation, was recruited to microirradiated sites. Importantly, the levels of the studied splicing factors were not changed by UVA light. Overall, if the appearance of m6A RNAs at DNA lesions is regulated enzymatically, this process must be mediated via the coregulatory function of METTL-like enzymes. This event is additionally accompanied by radiation-induced depletion of 2,2,7-methylguanosine (m3G/TMG) in RNA. Moreover, UV-irradiation also decreases the global cellular level of N1-methyladenosine (m1A) in RNAs. Based on these results, we prefer a model in which m6A RNAs rapidly respond to radiation-induced stress and diffuse to the damaged sites. The level of both (m1A) RNAs and m3G/TMG in RNAs is reduced as a consequence of DNA damage, recognized by the nucleotide excision repair mechanism.

译文

DNA损伤反应是由DNA修复蛋白和表观遗传标记介导的。在这里,我们观察到N6-methyladenosine (m6A) 是表位组的标志,在紫外线受损的染色质处积累的RNA中很常见; 然而,RNA聚合酶I和II的抑制剂不影响辐照基因组区域的m6A RNA水平。基因组损伤后,m6A rna扩散到受损的染色质中或以酶促的方式出现在病变处。DNA损伤不会改变METTL3和METTL14甲基转移酶的水平。在受照射的细胞的子集中,只有负责非编码rna中的m6A以及剪接调节的METTL16酶被募集到微照射位点。重要的是,所研究的拼接因子的水平不会因UVA光而改变。总体而言,如果通过酶调节DNA损伤处m6A rna的出现,则该过程必须通过METTL样酶的共调节功能来介导。该事件还伴随着辐射诱导的RNA中2,2,7-甲基鸟苷 (m3G/TMG) 的耗尽。此外,紫外线照射还降低了rna中N1-methyladenosine (m1A) 的整体细胞水平。基于这些结果,我们更喜欢m6A rna快速响应辐射诱导的压力并扩散到受损部位的模型。由于DNA损伤,rna中 (m1A) rna和m3G/TMG的水平均降低,这被核苷酸切除修复机制所识别。

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