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Nucleic Acids Research, 2003, Vol. 31, No. 4 1216-1223
© 2003 Oxford University Press

A single-nucleotide natural variation (U4 to C4) in an influenza A virus promoter exhibits a large structural change: implications for differential viral RNA synthesis by RNA-dependent RNA polymerase

Mi-Kyung Lee, Sung-Hun Bae, Chin-Ju Park, Hae-Kap Cheong1, Chaejoon Cheong1 and Byong-Seok Choi*

Department of Chemistry and National Creative Research Initiative Center, Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejon 305-701, Korea and 1 Magnetic Resonance Team, Korea Basic Science Institute, 52 Eoun-dong, Yuseong-gu, Daejon 305-333, Korea

*To whom correspondence should be addressed. Tel: +82 42 869 2828; Fax: +82 42 869 2810; Email: bschoi{at}cais.kaist.ac.kr

The influenza A virus promoter is recognized by the influenza A virus RNA-dependent RNA polymerase, and directs both transcription and replication of the viral RNA genome. Within the sequence of this promoter, flu strains exhibit a natural, unique variation, either a U or a C, at the fourth position from the 3' end. Promoters that contain a C residue (C4 promoter), which are invariably found in genome segments that encode the three RNA polymerase subunits (PB1, PB2 and PA), down-regulate transcription but activate genome replication. Here, we have determined the structure of the C4 promoter by NMR spectroscopy and compared it with the structure of the U4 promoter, which was determined previously. The structure of the internal loop in the C4 promoter is similar to that of the U4 promoter. However, the terminal stem of the C4 promoter is strikingly different from that of the U4 promoter. These structural data suggest that the internal loop is important for polymerase binding to the promoter, and the terminal stem is crucial for differential regulation of transcription and replication.


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