SURPRISING FUNCTION OF THE 3 INFLUENZA VIRAL POLYMERASE PROTEINS - SELECTIVE PROTECTION OF VIRAL MESSENGER-RNAS AGAINST THE CAP-SNATCHING REACTION CATALYZED BY THE SAME POLYMERASE PROTEINS

Influenza virus. a negative strand RNA virus, cannibalizes host cell, capped RNA polymerase It transcripts in the nucleus via a process term ed ''cap-snatching.'' The viral transcriptase enzyme, which is compose d of a complex of the three Viral polymerase (P) proteins, contains a cap-dependent endonuclease that cleaves capped cellular RNAs in the nu cleus 10-13 nucleotides from their 5' ends, The resulting capped RNA f ragments are required as primers for the initiation of viral mRNA synt hesis. In the 18 years since the discovery of ''cap-snatching'' it has not been determined how the viral transcriptase exhibits selectivity and ''snatches'' caps from cellular, but not viral, mRNAs. Here we elu cidate the surprising mechanism of this selectivity: the complex of th e same three viral P proteins that catalyzes ''cap-snatching'' is also responsible for selectivity protecting the 5' ends of viral, but not cellular, mRNAs from ''cap-snatching.'' The viral P protein complex is able to acquire these two very different functions because this compl ex lacks any detectable activity unless it binds to one or more specif ic RNA sequences. Here we demonstrate that the viral P protein complex binds to the common sequence in all the Viral mRNAs that is immediate ly 3' to the 5' sequence that is ''snatched'' from host cell RNAs. Thi s binding activates the cap-binding activity of the P protein complex thereby enhancing its binding to the capped vital mRNA We show that th ese P protein complexes protect the 5' ends of viral mRNAs from endonu cleolytic cleavage by the viral transcriptase, whereas the 5' ends of nonviral mRNAs are not protected. (C) 1996 Academic Press, Inc.