Structural features of an influenza virus promoter and their implications for viral RNA synthesis

The influenza A virus, a severe pandemic pathogen, has a segmented RNA geno me consisting of eight single-stranded RNA molecules. The 5 ' and 3 ' ends of each RNA segment recognized by the influenza A virus RNA-dependent RNA p olymerase direct both transcription and replication of the virus's RNA geno me. Promoter binding by the viral RNA polymerase and formation of an active open complex are prerequisites for viral replication and proliferation. He re, we describe the solution structure of this promoter as solved by multid imensional, heteronuclear magnetic resonance spectroscopy. Our studies show that the viral promoter has a significant dynamic nature and reveal an unu sual displacement of an adenosine that forms a novel (A-A).U motif and a C- A mismatch stacked in a, helix. The characterized structural features of th e promoter imply that the specificity of polymerase binding results from an internal RNA loop. In addition, an unexpected bending (46 +/- 10 degrees) near the initiation site suggests the existence of a promoter recognition m echanism similar to that of DNA-dependent,RNA polymerase and a possible reg ulatory function for the terminal structure during open complex formation.