ABCE1 Acts as a Positive Regulator of Exogenous RNA Decay.

Takuto Nogimori,Ryoya Goda,Yoshiaki Kitamura,Nao Hosoda,Yukio Kitade,Shin-Ichi Hoshino,Yuka Oishi,Koichi Ogami

doi:10.3390/v12020174

Abstract

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.

Highlights

The innate immune system is made of host defenses against infection that can be activated immediately by recognizing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs)
Our results indicate that ATP-binding cassette sub-family E member 1 (ABCE1) acts as a positive regulator of exogenous RNA decay rather than an inhibitor of RNase L
We demonstrated that ABCE1 directly binds Pelota and RNase L to function as a positive regulator of exogenous RNA decay

Summary

Introduction

The innate immune system is made of host defenses against infection that can be activated immediately by recognizing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The innate immune system depends on interferon (IFN)-signaling pathways. Among the first discovered IFN-induced antiviral defense mechanisms, the canonical 20 -50 -oligoadenylate synthetase (OAS)/RNase L system is an RNA cleavage pathway that responds to viral dsRNAs as PAMPs [1,2]. In response to the dsRNAs, OAS produces a unique oligonucleotide 20 -50 oligoadenylates (2–5A), which acts as a second messenger to trigger dimerization and activation of latent RNase L. RNase L endonuclease cleaves viral single-stranded RNA and limits viral replication [3,4]. An RNA quality control factor Dom34/Pelota was identified as a restriction factor for a positive-sense single stranded RNA virus [5].

Methods

Results

Conclusion