State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China.
BMC Plant Biol. 2022 Dec 12;22(1):576. doi: 10.1186/s12870-022-03951-9.
MicroRNAs (miRNAs) and other epigenetic modifications play fundamental roles in all eukaryotic biological processes. DNA damage repair is a key process for maintaining the genomic integrity of different organisms exposed to diverse stresses. However, the reaction of miRNAs in the DNA damage repair process is unclear.
In this study, we found that the simultaneous mutation of zinc finger DNA 3'-phosphoesterase (ZDP) and AP endonuclease 2 (APE2), two genes that play overlapping roles in active DNA demethylation and base excision repair (BER), led to genome-wide alteration of miRNAs. The transcripts of newly transcribed miRNA-encoding genes (MIRs) decreased significantly in zdp/ape2, indicating that the mutation of ZDP and APE2 affected the accumulation of miRNAs at the transcriptional level. In addition, the introduction of base damage with the DNA-alkylating reagent methyl methanesulfonate (MMS) accelerated the reduction of miRNAs in zdp/ape2. Further mutation of FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE (FPG), a bifunctional DNA glycosylase/lyase, rescued the accumulation of miRNAs in zdp/ape2, suggesting that the accumulation of DNA damage repair intermediates induced the transcriptional repression of miRNAs.
Our investigation indicates that the accumulation of DNA damage repair intermediates inhibit miRNAs accumulation by inhibiting MIR transcriptions.
微小 RNA(miRNAs)和其他表观遗传修饰在所有真核生物过程中发挥着基本作用。DNA 损伤修复是维持不同生物体基因组完整性的关键过程,使其能够应对各种应激。然而,miRNAs 在 DNA 损伤修复过程中的反应尚不清楚。
在这项研究中,我们发现锌指 DNA 3′-磷酸酯酶(ZDP)和 AP 内切核酸酶 2(APE2)这两个基因的同时突变,这两个基因在主动 DNA 去甲基化和碱基切除修复(BER)中发挥重叠作用,导致 miRNA 发生全基因组改变。新转录 miRNA 编码基因(MIRs)的转录物在 zdp/ape2 中显著减少,表明 ZDP 和 APE2 的突变影响了 miRNA 在转录水平上的积累。此外,用 DNA-烷化试剂甲磺酸甲酯(MMS)引入碱基损伤加速了 zdp/ape2 中 miRNA 的减少。进一步突变双功能 DNA 糖苷酶/裂解酶 FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE(FPG),挽救了 zdp/ape2 中 miRNA 的积累,表明 DNA 损伤修复中间体的积累诱导了 miRNA 的转录抑制。
我们的研究表明,DNA 损伤修复中间体的积累通过抑制 MIR 转录来抑制 miRNA 的积累。