The RNase L inhibitor (RLI) is induced by double-stranded RNA.
The (2-5A)-RNase L pathway is an important component of interferon (IFN) action. Its central role in the antiviral effect of IFN against Picornaviridae has been clearly demonstrated. We have characterized and cloned a new component of this pathway, the RNase L inhibitor (RLI). RLI is a cellular protein whose mRNA is not regulated by IFN but is induced by viruses, such as encephalomyocarditis virus (EMCV). RLI inhibits RNase L during the time course of EMCV infection, and overexpression of RLI in HeLa cells partially reverses the antiviral action of IFN against EMCV. The replicative complexes of several viruses consist of double-stranded RNA structures. These dsRNAs could activate gene transcription as demonstrated for IFNs and could be responsible for RLI induction. We describe the increased expression of RLI mRNA and RLI protein induced by synthetic dsRNAs, such as poly(I):poly(C). This induction gives rise to an inhibition of the 2-5A-binding activity of RNase L. The inhibition of RNase L activity is transcient, probably due to the rapid turnover of RLI protein.
Martinand
C
C
IGMM UMR-CNRS 5535-Université Montpellier II, France.
Salehzada
T
T
Silhol
M
M
Lebleu
B
B
Bisbal
C
C
D018528:ATP-Binding Cassette Transporters; D002460:Cell Line; D018833:Chaperonins; D003001:Cloning, Molecular; D004686:Encephalomyocarditis virus / Q000502:physiology; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000302:isolation & purification / Q000493:pharmacokinetics; D012330:RNA, Double-Stranded / Q000096:biosynthesis*; D014779:Virus Replication
C501917:ABCE1 protein, human; D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D011506:Proteins; D012330:RNA, Double-Stranded; D018833:Chaperonins