Abstract
Capped ribopolymers lacking a sequence complementary to the common 3' end of the influenza virion RNA segments effectively stimulated transcription of these RNAs by the virion-associated transcriptase. Thus, stimulation of transcription results not from hydrogen bonding between the capped RNA and the 3' end of the virion RNA but presumably from a specific interaction of the capped RNA with protein(s) in the transcriptase complex. Although no specific nucleotide sequence was required for priming activity, capped mRNAs with diminished secondary structure were preferred as primers. Inosine-substituted or bisulfite-modified capped reovirus mRNAs were at least 3- to 5-fold more effective as primers than were the native capped mRNAs. On the other hand, inosine substitution or bisulfite treatment of the uncapped form of reovirus mRNAs converted them from essentially inactive species to potent inhibitors of the transcriptase reaction primed by either ApG or globin mRNA. These effects of reduced secondary structure also most probably reflect an interaction of the exogenous RNAs with transcriptase protein(s). The results obtained from screening a series of native uncapped ribopolymers were consistent with inhibitory activity requiring the absence of most hydrogen bonding in the ribopolymer and also suggested that specific structural feature(s) of the nucleotides in the chain were important.
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- Both G. W., Furuichi Y., Muthukrishnan S., Shatkin A. J. Effect of 5'-terminal structure and base composition on polyribonucleotide binding to ribosomes. J Mol Biol. 1976 Jul 5;104(3):637–658. doi: 10.1016/0022-2836(76)90126-1. [DOI] [PubMed] [Google Scholar]
- Bouloy M., Morgan M. A., Shatkin A. J., Krug R. M. Cap and internal nucleotides of reovirus mRNA primers are incorporated into influenza viral complementary RNA during transcription in vitro. J Virol. 1979 Dec;32(3):895–904. doi: 10.1128/jvi.32.3.895-904.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bouloy M., Plotch S. J., Krug R. M. Both the 7-methyl and the 2'-O-methyl groups in the cap of mRNA strongly influence its ability to act as primer for influenza virus RNA transcription. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3952–3956. doi: 10.1073/pnas.77.7.3952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bouloy M., Plotch S. J., Krug R. M. Globin mRNAs are primers for the transcription of influenza viral RNA in vitro. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4886–4890. doi: 10.1073/pnas.75.10.4886. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHAMBERLIN M., BALDWIN R. L., BERG P. AN ENZYMICALLY SYNTHESIZED RNA OF ALTERNATING BASE SEQUENCE: PHYSICAL AND CHEMICAL CHARACTERIZATION. J Mol Biol. 1963 Oct;7:334–349. doi: 10.1016/s0022-2836(63)80028-5. [DOI] [PubMed] [Google Scholar]
- England T. E., Uhlenbeck O. C. 3'-terminal labelling of RNA with T4 RNA ligase. Nature. 1978 Oct 12;275(5680):560–561. doi: 10.1038/275560a0. [DOI] [PubMed] [Google Scholar]
- Furuichi Y., Shatkin A. J. 5'-termini of reovirus mRNA: ability of viral cores to form caps post-transcriptionally. Virology. 1977 Apr;77(2):566–578. doi: 10.1016/0042-6822(77)90482-2. [DOI] [PubMed] [Google Scholar]
- Furuichi Y., Shatkin A. J. Differential synthesis of blocked and unblocked 5'-termini in reovirus mRNA: effect of pyrophosphate and pyrophosphatase. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3448–3452. doi: 10.1073/pnas.73.10.3448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koper-Zwarthoff E. C., Lockard R. E., Alzner-deWeerd B., RajBhandary U. L., Bol J. F. Nucleotide sequence of 5' terminus of alfalfa mosaic virus RNA 4 leading into coat protein cistron. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5504–5508. doi: 10.1073/pnas.74.12.5504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozak M. Influence of mRNA secondary structure on binding and migration of 40S ribosomal subunits. Cell. 1980 Jan;19(1):79–90. doi: 10.1016/0092-8674(80)90390-6. [DOI] [PubMed] [Google Scholar]
- Krug R. M., Broni B. A., Bouloy M. Are the 5' ends of influenza viral mRNAs synthesized in vivo donated by host mRNAs? Cell. 1979 Oct;18(2):329–334. doi: 10.1016/0092-8674(79)90052-7. [DOI] [PubMed] [Google Scholar]
- McGeoch D., Kitron N. Influenza virion RNA-dependent RNA polymerase: stimulation by guanosine and related compounds. J Virol. 1975 Apr;15(4):686–695. doi: 10.1128/jvi.15.4.686-695.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Michelson A. M., Massoulié J., Guschlbauer W. Synthetic polynucleotides. Prog Nucleic Acid Res Mol Biol. 1967;6:83–141. doi: 10.1016/s0079-6603(08)60525-5. [DOI] [PubMed] [Google Scholar]
- Plotch S. J., Bouloy M., Krug R. M. Transfer of 5'-terminal cap of globin mRNA to influenza viral complementary RNA during transcription in vitro. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1618–1622. doi: 10.1073/pnas.76.4.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plotch S. J., Krug R. M. Influenza virion transcriptase: synthesis in vitro of large, polyadenylic acid-containing complementary RNA. J Virol. 1977 Jan;21(1):24–34. doi: 10.1128/jvi.21.1.24-34.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plotch S. J., Tomasz J., Krug R. M. Absence of detectable capping and methylating enzymes in influenza virions. J Virol. 1978 Oct;28(1):75–83. doi: 10.1128/jvi.28.1.75-83.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson H. D., Dickson E., Plotch S. J., Krug R. M. Identification of the RNA region transferred from a representative primer, beta-globin mRNA, to influenza mRNA during in vitro transcription. Nucleic Acids Res. 1980 Mar 11;8(5):925–942. doi: 10.1093/nar/8.5.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson J. S. 5' and 3' terminal nucleotide sequences of the RNA genome segments of influenza virus. Nucleic Acids Res. 1979 Aug 24;6(12):3745–3757. doi: 10.1093/nar/6.12.3745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shatkin A. J., LaFiandra A. J. Transcription by infectious subviral particles of reovirus. J Virol. 1972 Oct;10(4):698–706. doi: 10.1128/jvi.10.4.698-706.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skehel J. J., Hay A. J. Nucleotide sequences at the 5' termini of influenza virus RNAs and their transcripts. Nucleic Acids Res. 1978 Apr;5(4):1207–1219. doi: 10.1093/nar/5.4.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith J. C., Raper R. H., Bell L. D., Stebbing N., McGeoch D. Inhibition of influenza virion transcriptases by polynucleotides. Virology. 1980 May;103(1):245–249. doi: 10.1016/0042-6822(80)90144-0. [DOI] [PubMed] [Google Scholar]
- Sonenberg N., Rupprecht K. M., Hecht S. M., Shatkin A. J. Eukaryotic mRNA cap binding protein: purification by affinity chromatography on sepharose-coupled m7GDP. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4345–4349. doi: 10.1073/pnas.76.9.4345. [DOI] [PMC free article] [PubMed] [Google Scholar]