Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Viruses. 2020 Feb 4;12(2):174. doi: 10.3390/v12020174.
The 2'-5'-oligoadenylate synthetase (OAS)/RNase L system protects hosts against pathogenic viruses through cleavage of the exogenous single-stranded RNA. In this system, an evolutionally conserved RNA quality control factor Dom34 (known as Pelota (Pelo) in higher eukaryotes) forms a surveillance complex with RNase L to recognize and eliminate the exogenous RNA in a manner dependent on translation. Here, we newly identified that ATP-binding cassette sub-family E member 1 (ABCE1), which is also known as RNase L inhibitor (RLI), is involved in the regulation of exogenous RNA decay. ABCE1 directly binds to form a complex with RNase L and accelerates RNase L dimer formation in the absence of 2'-5' oligoadenylates (2-5A). Depletion of ABCE1 represses 2-5A-induced RNase L activation and stabilizes exogenous RNA to a level comparable to that seen in RNase L depletion. The increased half-life of the RNA by the single depletion of either protein is not significantly affected by the double depletion of both proteins, suggesting that RNase L and ABCE1 act together to eliminate exogenous RNA. Our results indicate that ABCE1 functions as a positive regulator of exogenous RNA decay rather than an inhibitor of RNase L.
2'-5'-寡聚腺苷酸合成酶 (OAS)/核糖核酸酶 L 系统通过切割外源单链 RNA 来保护宿主免受致病病毒的侵害。在该系统中，一种进化上保守的 RNA 质量控制因子 Dom34（在高等真核生物中称为 Pelota (Pelo)）与 RNase L 形成一个监视复合物，以依赖翻译的方式识别和消除外源 RNA。在这里，我们新发现 ATP 结合盒亚家族 E 成员 1（ABCE1），也称为核糖核酸酶 L 抑制剂（RLI），参与调节外源 RNA 的降解。ABCE1 直接与 RNase L 结合形成复合物，并在没有 2'-5'寡聚腺苷酸 (2-5A) 的情况下加速 RNase L 二聚体的形成。ABCE1 的耗竭抑制了 2-5A 诱导的 RNase L 激活，并使外源 RNA 稳定到与 RNase L 耗竭相当的水平。这两种蛋白质中的任一种单独耗竭对 RNA 半衰期的影响都不显著，这表明 RNase L 和 ABCE1 共同作用以消除外源 RNA。我们的结果表明，ABCE1 作为外源 RNA 降解的正调节剂发挥作用，而不是 RNase L 的抑制剂。
