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EMBO J. Oct 1991; 10(10): 2941–2947.
PMCID: PMC453008

Poliovirus proteinase 3C converts an active form of transcription factor IIIC to an inactive form: a mechanism for inhibition of host cell polymerase III transcription by poliovirus.


In HeLa cells, RNA polymerase III (pol III)-mediated transcription is severely inhibited by poliovirus infection. This is due primarily to a reduction in the transcriptional activity of TFIIIC, a transcription factor which binds in a sequence specific manner to the internal promoter of pol III genes. Using gel retardation assays, we have shown previously that inhibition of pol III transcription by poliovirus is correlated with disappearance of a transcriptionally active form of TFIIIC (complex I) concomitant with the appearance of a faster mobility, transcriptionally inactive form of TFIIIC (complex III). We show here that a poliovirus with a point mutation in the proteinase 3C (3Cpro) region failed to produce complex III and is limited in its ability to inhibit pol III transcription compared with the wild-type virus. Incubation of purified 3Cpro, expressed in Escherichia coli, with transcriptionally active TFIIIC (complex I) in vitro resulted in generation of the transcriptionally inactive complex III form of TFIIIC. In an in vitro transcription assay, treatment of the complex I form of TFIIIC with 3Cpro almost completely inhibited pol III transcription. Finally expression of the 3Cpro gene in transfected HeLa cells resulted in significant inhibition of pol III-mediated transcription. The results presented here suggest that proteolysis of the transcriptionally active form of TFIIIC by poliovirus 3Cpro is a mechanism by which poliovirus inhibits host cell RNA pol III transcription.

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  • Urzainqui A, Carrasco L. Degradation of cellular proteins during poliovirus infection: studies by two-dimensional gel electrophoresis. J Virol. 1989 Nov;63(11):4729–4735. [PMC free article] [PubMed]
  • ZIMMERMAN EF, HEETER M, DARNELL JE. RNA synthesis in poliovirus-infected cells. Virology. 1963 Mar;19:400–408. [PubMed]
  • Andino R, Rieckhof GE, Baltimore D. A functional ribonucleoprotein complex forms around the 5' end of poliovirus RNA. Cell. 1990 Oct 19;63(2):369–380. [PubMed]
  • BALTIMORE D, FRANKLIN RM. The effect of Mengovirus infection on the activity of the DNA-dependent RNA polymerase of L-cells. Proc Natl Acad Sci U S A. 1962 Aug;48:1383–1390. [PMC free article] [PubMed]
  • Clark ME, Dasgupta A. A transcriptionally active form of TFIIIC is modified in poliovirus-infected HeLa cells. Mol Cell Biol. 1990 Oct;10(10):5106–5113. [PMC free article] [PubMed]
  • Crawford N, Fire A, Samuels M, Sharp PA, Baltimore D. Inhibition of transcription factor activity by poliovirus. Cell. 1981 Dec;27(3 Pt 2):555–561. [PubMed]
  • Dasgupta A. Purification of host factor required for in vitro transcription of poliovirus RNA. Virology. 1983 Jul 15;128(1):245–251. [PubMed]
  • Dewalt PG, Semler BL. Site-directed mutagenesis of proteinase 3C results in a poliovirus deficient in synthesis of viral RNA polymerase. J Virol. 1987 Jul;61(7):2162–2170. [PMC free article] [PubMed]
  • Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. [PMC free article] [PubMed]
  • Falk MM, Grigera PR, Bergmann IE, Zibert A, Multhaup G, Beck E. Foot-and-mouth disease virus protease 3C induces specific proteolytic cleavage of host cell histone H3. J Virol. 1990 Feb;64(2):748–756. [PMC free article] [PubMed]
  • Fernández-Tomás C. The presence of viral-induced proteins in nuclei from poliovirus-infected HeLa cells. Virology. 1982 Jan 30;116(2):629–634. [PubMed]
  • Fradkin LG, Yoshinaga SK, Berk AJ, Dasgupta A. Inhibition of host cell RNA polymerase III-mediated transcription by poliovirus: inactivation of specific transcription factors. Mol Cell Biol. 1987 Nov;7(11):3880–3887. [PMC free article] [PubMed]
  • Garcia JA, Harrich D, Pearson L, Mitsuyasu R, Gaynor RB. Functional domains required for tat-induced transcriptional activation of the HIV-1 long terminal repeat. EMBO J. 1988 Oct;7(10):3143–3147. [PMC free article] [PubMed]
  • Geiduschek EP, Tocchini-Valentini GP. Transcription by RNA polymerase III. Annu Rev Biochem. 1988;57:873–914. [PubMed]
  • Hämmerle T, Hellen CU, Wimmer E. Site-directed mutagenesis of the putative catalytic triad of poliovirus 3C proteinase. J Biol Chem. 1991 Mar 25;266(9):5412–5416. [PubMed]
  • Hellen CU, Kräusslich HG, Wimmer E. Proteolytic processing of polyproteins in the replication of RNA viruses. Biochemistry. 1989 Dec 26;28(26):9881–9890. [PubMed]
  • Hoeffler WK, Kovelman R, Roeder RG. Activation of transcription factor IIIC by the adenovirus E1A protein. Cell. 1988 Jun 17;53(6):907–920. [PubMed]
  • Käriäinen L, Ranki M. Inhibition of cell functions by RNA-virus infections. Annu Rev Microbiol. 1984;38:91–109. [PubMed]
  • Kliewer S, Dasgupta A. An RNA polymerase II transcription factor inactivated in poliovirus-infected cells copurifies with transcription factor TFIID. Mol Cell Biol. 1988 Aug;8(8):3175–3182. [PMC free article] [PubMed]
  • Kräusslich HG, Wimmer E. Viral proteinases. Annu Rev Biochem. 1988;57:701–754. [PubMed]
  • Lee KA, Bindereif A, Green MR. A small-scale procedure for preparation of nuclear extracts that support efficient transcription and pre-mRNA splicing. Gene Anal Tech. 1988 Mar-Apr;5(2):22–31. [PubMed]
  • Nicklin MJ, Harris KS, Pallai PV, Wimmer E. Poliovirus proteinase 3C: large-scale expression, purification, and specific cleavage activity on natural and synthetic substrates in vitro. J Virol. 1988 Dec;62(12):4586–4593. [PMC free article] [PubMed]
  • Rubinstein SJ, Dasgupta A. Inhibition of rRNA synthesis by poliovirus: specific inactivation of transcription factors. J Virol. 1989 Nov;63(11):4689–4696. [PMC free article] [PubMed]
  • Schwartz LB, Lawrence C, Thach RE, Roeder RG. Encephalomyocarditis virus infection of mouse plasmacytoma cells. II. Effect on host RNA synthesis and RNA polymerases. J Virol. 1974 Sep;14(3):611–619. [PMC free article] [PubMed]
  • Segall J, Matsui T, Roeder RG. Multiple factors are required for the accurate transcription of purified genes by RNA polymerase III. J Biol Chem. 1980 Dec 25;255(24):11986–11991. [PubMed]
  • Sonenberg N. Poliovirus translation. Curr Top Microbiol Immunol. 1990;161:23–47. [PubMed]
  • Tesar M, Marquardt O. Foot-and-mouth disease virus protease 3C inhibits cellular transcription and mediates cleavage of histone H3. Virology. 1990 Feb;174(2):364–374. [PubMed]

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