ABCE1 Acts as a Positive Regulator of Exogenous RNA Decay

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.

Down-regulation of ABCE1 inhibits temozolomide resistance in glioma through the PI3K/Akt/NF-κB signaling pathway

The ATP binding cassette (ABC) E1 (ABCE1), a member of the ABC family, was originally described as the RNase L inhibitor. Through forming a heterodimer with RNase L, ABCE1 participates in the negative regulation of the 2-5A/RNase L system and thus mediates a wide range of biological functions. Recent evidence has shown the new roles of ABCE1 in tumorigenesis. However, there have been no investigations on the specific effect of ABCE1 on glioma. In the present study, we examined the expression pattern and possible role of ABCE1 in glioma. Our study demonstrated that ABCE1 was up-regulated in glioma tissues and cell lines. Down-regulation of ABCE1 inhibited temozolomide (TMZ) resistance of glioma cells in vitro and in vivo. In addition, we found that the PI3K/Akt/NF-κB pathway was involved in ABCE1-mediated chemoresistance of glioma cells. Taken together, our study suggested ABCE1 as a promising target for glioma chemotherapy.