Picornavirus 2A Proteinase-Mediated Stimulation of Internal Initiation of Translation Is Dependent on Enzymatic Activity and the Cleavage Products of Cellular Proteins

Poliovirus and human rhinovirus 2A proteinases are known to stimulate translation initiation on the cognate viral Internal Ribosome Entry Segments (IRESes). The molecular mechanism of this translational transactivation was investigated in vitro using dicistronic mRNAs containing picornaviral IRESes...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 1995-11, Vol.213 (2), p.549-557
Main Authors: ZlEGLER, E., BORMAN, A.M., DELIAT, F.G., LIEBIG, H-D., JUGOVIC, D., KEAN, K.M., SKERN, T., KUECHLER, E.
Format: Article
Language:English
Subjects:
Base Sequence
Cardiovirus - metabolism
Cysteine Endopeptidases - metabolism
DNA, Complementary
Enterovirus - enzymology
Enterovirus - genetics
HeLa Cells
Humans
Molecular Sequence Data
Protein Biosynthesis
Proteins - metabolism
Rhinovirus - enzymology
Rhinovirus - genetics
RNA, Messenger - genetics
RNA, Viral - genetics
Viral Proteins - biosynthesis
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Summary:Poliovirus and human rhinovirus 2A proteinases are known to stimulate translation initiation on the cognate viral Internal Ribosome Entry Segments (IRESes). The molecular mechanism of this translational transactivation was investigated in vitro using dicistronic mRNAs containing picornaviral IRESes as the intercistronic spacer and purified human rhinovirus type 2 and coxsackievirus B4 2A proteinases. The stimulation achieved on the HRV2 IRES in the presence of the cognate 2A proteinase at 1 microgram/ml was twofold; the maximum stimulation at 100 micrograms/ml was fivefold. The IRESes and proteinases from rhino- and enteroviruses were interchangeable; however, stimulation of translation initiation on a cardiovirus IRES by these proteinases was minimal. Studies using an inhibitor or a mutant 2A proteinase demonstrated that translation stimulation requires 2A-mediated enzymatic conversion of some cellular component(s). The HRV2 2A proteinase also stimulated translation initiation on full-length viral RNA, suggesting that 2A proteinase-mediated stimulation of IRES-driven translation has a physiological role.
ISSN:0042-6822
1096-0341
DOI:10.1016/S0042-6822(95)90001-2