Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human hepatitis C virus (HCV) contains a long 5' noncoding region (5' NCR). Computer-assisted and biochemical analyses suggest that there is a complex secondary structure in this region that is comparable to the secondary structures that are found in picornaviruses (E.A. Brown, H. Zhang, L.-H. Ping, and S.M. Lemon, Nucleic Acids Res. 20:5041-5045, 1992). Previous in vitro studies suggest that the HCV 5' NCR plays an important role during translation (K. Tsukiyama-Kohara, N. Iizuka, M. Kohara, and A. Nomoto, J. Virol. 66:1476-1483, 1992). Dicistronic and monocistronic expression vectors, in vitro translation, RNA transfections, and deletion mutagenesis studies were utilized to demonstrate unambiguously that the HCV 5' NCR is involved in translational control. Our data strongly support the conclusion that an internal ribosome entry site exists within the 5' noncoding sequences proximal to the initiator AUG. Furthermore, our results suggest that the HCV genome is translated in a cap-independent manner and that the sequences immediately upstream of the initiator AUG are essential for internal ribosome entry site function during translation.
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PMID:Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism. 838 3

Translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry through the 5' end (5' noncoding region) in a cap-independent fashion. The relatively long stretch of this noncoding region contains multiple initiation codons that are apparently not used for translation. Translation of the HCV polyprotein is initiated instead from an AUG located at nt 342. Using computer-assisted analysis (and subsequently substantiated by enzymatic probing), a complex secondary and tertiary structure of the 5' noncoding region (5'NCR) has been predicted. Based on an RNA folding model proposed by Brown et al. (1992), a detailed mutational analysis carried out identified the key secondary structural regions that are of functional significance in translational control. Maintenance of a helical structural element relevant to an oligopyrimidine tract is essential for internal initiation. A putative coaxial stacking or a pseudoknot structure upstream of the initiator AUG seems to be central to an internal ribosome entry site (IRES)-mediated translation of the HCV RNA genome.
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PMID:Translation of hepatitis C virus genome. 887 14