Department of Microbiology, Oslo University Hospital HF and University of Oslo, Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway.
Nat Commun. 2013;4:2271. doi: 10.1038/ncomms3271.
Endonuclease V orthologues are highly conserved proteins found in all kingdoms of life. While the prokaryotic enzymes are DNA repair proteins for removal of deaminated adenosine (inosine) from the genome, no clear role for the eukaryotic counterparts has hitherto been described. Here we report that human endonuclease V (ENDOV) and also Escherichia coli endonuclease V are highly active ribonucleases specific for inosine in RNA. Inosines are normal residues in certain RNAs introduced by specific deaminases. Adenosine-to-inosine editing is essential for proper function of these transcripts and defects are linked to various human disease. Here we show that human ENDOV cleaves an RNA substrate containing inosine in a position corresponding to a biologically important site for deamination in the Gabra-3 transcript of the GABA(A) neurotransmitter. Further, human ENDOV specifically incises transfer RNAs with inosine in the wobble position. This previously unknown RNA incision activity may suggest a role for endonuclease V in normal RNA metabolism.
内切核酸酶 V 同源物是在所有生命领域中高度保守的蛋白质。虽然原核酶是用于从基因组中去除脱氨腺嘌呤（肌苷）的 DNA 修复蛋白，但迄今尚未描述真核酶的明确作用。在这里，我们报告人类内切核酸酶 V（ENDOV）和大肠杆菌内切核酸酶 V 是高度活跃的核糖核酸内切酶，专门针对 RNA 中的肌苷。肌苷是某些由特定脱氨酶引入的 RNA 中的正常残基。腺嘌呤到肌苷的编辑对于这些转录本的正常功能至关重要，缺陷与各种人类疾病有关。在这里，我们表明人类 ENDOV 在对应于 GABA(A)神经递质 Gabra-3 转录物中脱氨酶的生物重要位置的位置切割含有肌苷的 RNA 底物。此外，人类 ENDOV 特异性切割在摆动位置含有肌苷的转移 RNA。这种先前未知的 RNA 切口活性可能表明内切核酸酶 V 在正常 RNA 代谢中的作用。
