Binding of Glycyl-tRNA synthetase to the 3´UTR stimulates Mengovirus RNA translation

ABSTRACT: Picornaviruses are small viruses with a plus strand (i.e. mRNA orientation) RNA genome. Due to their limited coding capacity, these viruses use RNA secondary structures in their genomic RNAs like aptamers to bind cellular proteins. The resulting molecular interactions are then used to support translation and replication of the viral RNA. In this study, we have characterized a tRNA anticodon stem-loop-like structure in the 3´ untranslated region (3´UTR) of Mengovirus, a member of the Cardiovirus group in the Picornaviridae family. This RNA structure specifically binds to the cellular enzyme Glycyl-tRNA synthetase (GARS or GlyRS). Mutation of the conserved CCA motif in the loop of this GARS binding element (GBE) as well as deletion of the anticodon binding domain of GARS impair binding. Infection with a Mengovirus carrying a mutated GBE results in reduced replication in HeLa cells and in neuronal cells. Translation of the full length Mengovirus genome in HeLa cells is impaired by the GBE mutation directly after transfection, independent of the activity of the viral polymerase. Consistently, recruitment of translation elongation factors and ribosomes to translation reporter RNAs bearing the Mengovirus untranslated regions and translation efficiencies of these Mengovirus translation reporter RNAs are impaired by mutation of the GBE, while RNA stability is not affected. Thus, this conserved GARS binding element in the Mengovirus 3´UTR is involved in regulation of Mengovirus RNA translation likely on the elongation stage.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Viruses Mengo Virus

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: Uwe Linne  

LAB HEAD: Dr. Uwe Linne

PROVIDER: PXD057754 | Pride | 2025-12-03

REPOSITORIES: Pride