[Frontiers in Bioscience 3, d1241-1252, December 1, 1998]
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CAVEAT LECTOR




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INHIBITION OF INTERNAL ENTRY SITE (IRES)-MEDIATED TRANSLATION BY A SMALL YEAST RNA: A NOVEL STRATEGY TO BLOCK HEPATITIS C VIRUS PROTEIN SYNTHESIS

Saumitra Das1, Michael Ott2, Akemi Yamane1, Arun Venkatesan1, Sanjeev Gupta2 and Asim Dasgupta1

Department of Microbiology, Molecular Genetics and Immunolog, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095-17471 , 2Department of Medicine, Albert Einstein, College of Medicine of Yeshiva University, Bronx, New York 10461-1602

Received 9/18/98 Accepted 9/23/98

TABLE OF CONTENTS

1. Abstract

2. Introduction
2.1. Internal initiation of translation in eukaryotes
2.2. The structure of IRES-elements in different groups of viruses
2.3. Cellular proteins that interact with viral 5´UTR of viral RNAs
2.4. Requirement of canonical initiation factors in IRES-mediated translation
3. Translation of viral RNA in yeast
3.1. Poliovirus RNA is not translated in yeast
3.2. IRNA specifically inhibits IRES-mediated translation
3.3. Minimum sequences required for IRNA activity
3.4. Inhibition of HCV translation by IRNA in vivo and in vitro
3.5. Constitutive expression of IRNA in eukaryotic cells
3.6. Cells expressing IRNA are refractory to PV and PV/HCV chimera infection
3.7. IRNA binds proteins that are critical for HCV IRES mediated translation
4. Structure of IRNA
4.1. Structure of IRNA is important for its inhibitory activity
4.2. IRNA-encoding genes in S. cerevisiae
5. Perspective
6. Acknowledgments
7. References
8. Entire manuscript

Key words: IRES, HCV, Translation-inhibitor, Hepatitis, Hepatitis C, Hepatitis C virus, Virus, RNA, Protein synthesis