Influenza virus employs a novel mechanism for the synthesis of its viral mRNAs. Viral mRNA synthesis requires initiation by host cell primers, specifically capped (m7Gppp Nm-containing) RNA fragments derived from host cell RNA polymerase II transcripts (Plotch et al., 1979;Krug et al., , 1981. This occurs in the nucleus of the infected cells. Viral mRNA synthesis requires the continuous functioning of the cellular RNA polymerase II, and is therefore inhibited by α-amanitin. The host cell primers are generated by a viral cap-dependent endonuclease that cleaves the capped cellular RNAs 10-13 nucleotides from their 5′ ends, preferentially at a purine residue. Priming does not require hydrogen bonding between the capped primer fragments and the 3′-ends of the viral (v)RNA templates. Rather, priming requires the presence of a 5′-methylated cap structure. In fact, each of the methyl groups in the cap, the 2′-O-methyl on the penultimate base as well as the 7-methyl on the terminal G, strongly increase priming activity. Transcription is initiated by the incorporation of a G residue onto the 3′ end of the resulting fragments, directed by the penultimate C residue of the vRNAs. Viral mRNA chains are then elongated until a stretch of 4-7 uridine residues is reached, 17 to 22 nucleotides before the 5′ ends of the vRNAs, where transcription terminates and polyadenylate is added to the mRNAs. These capped short RNA fragments are potential inhibitors of cap-dependent transcription in vitro. A recent study has confirmed earlier data (Bouloy et al., 1978;Ulmanen et al., 1981;Braam et al., 1983;Kawakami et al., 1983;Kato et al., 1985) that suggest that priming by capped oligonucleotides can be uncoupled from the endonuclease activity of the influenza RNA polymerase, and has suggested the use of such inhibitors as decoys of cap-dependent transcription in vitro (Chung et al., 1994
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.