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Mutational analysis of a conserved tetraloop in the 5′ untranslated region of hepatitis C virus identifies a novel RNA element essential for the internal ribosome entry site function
Author(s) -
Psaridi L,
Georgopoulou U,
Varaklioti A,
Mavromara P
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00662-6
Subject(s) - internal ribosome entry site , five prime untranslated region , untranslated region , three prime untranslated region , biology , rna , eukaryotic translation , ribosome , stem loop , translation (biology) , nucleic acid structure , ribosomal binding site , genetics , virology , microbiology and biotechnology , messenger rna , gene
The 5′ untranslated region of hepatitis C virus RNA forms an extensive secondary structure including several hairpin motifs and mediates translation initiation by an internal ribosome entry site‐dependent pathway. We report, here, an extensive mutagenesis analysis of a highly conserved tetraloop in the 5′ untranslated region of hepatitis C virus, namely hairpin IIIe (295′‐GAUA‐298′). Our results demonstrate that hairpin IIIe is essential for the internal ribosome entry site function. Moreover, they indicate the importance of the primary structure of this motif because mutations in all four nucleotides of the loop caused a severe loss of internal ribosome entry site activity. These data represent the first experimental evidence for the functional significance of tetraloops in internal ribosome entry site‐driven translation of hepatitis C virus.