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Gene Review

pol  -  RNA-dependent DNA polymerase

Friend murine leukemia virus

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Disease relevance of pol


Psychiatry related information on pol


High impact information on pol

  • We have used in vitro mutagenesis to explore the functions of the gene products encoded by the pol gene of Moloney murine leukemia virus (M-MuLV) [7].
  • These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation [8].
  • Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env [8].
  • The Friend erythroleukemia cell line T3-C12, which produces Friend murine leukemia virus (F-MuLV) and can be induced to synthesize hemoglobin by dimethyl sulfoxide (DMSO), was monitored for viral RNA-dependent DNA polymerase reverse transcriptase (RT) activity [9].
  • Retroviruses whose gag and pol genes are in the same reading frame depend upon approximately 5% read-through of the gag UAG termination codon to make the gag-pol polyprotein [10].

Chemical compound and disease context of pol


Biological context of pol

  • This DNA fragment encompassed approximately 700 base pairs from the 3' end of the F-MuLV pol gene and 1.7 kilobase pairs of the env gene including all of gp70 and the N-terminal four-fifths of p15E [14].
  • Two factors were found in the U3, and R-U5-5'-non-coding regions, and at least two factors in the gag gene region that contained the N-terminal part of the pol gene [15].
  • To construct the expression vector, pA8(Psi-), which expresses the genes gag, pol and env derived from A8-V, the SV40 early region was used for the polyadenylation signal (polyA signal) [16].
  • However, some regions of the genome showed some homology to retroviral gag and pol open reading frames [17].
  • We localized the primary leukemogenic determinant to a 3.8-kilobase fragment of the SL3-3 genome containing the viral long terminal repeat, 5' untranslated sequences, gag gene, and 5', 30% of the pol gene [18].

Anatomical context of pol

  • We have previously shown that strong epitopes recognized by anti-Friend virus (FV) cytotoxic T lymphocytes (CTL) in H-2b mice are encoded in both the env and gag/pol regions of the helper friend leukemia virus genome [19].
  • The plasmid containing the gag and pol genes and the plasmid containing the env gene were cotransfected into NIH 3T3 cells [20].
  • Approximately 5% of the ribosomes translating the gag gene of murine leukemia viruses read through the UAG terminator and translate the in-frame pol gene to produce the gag-pol fusion polyprotein, the sole source of the pol gene products [21].
  • The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 10(5) colony-forming units per ml [22].

Associations of pol with chemical compounds

  • Intermediate reverse transcriptase precursor Pr125pol lacked peptide sequences of the four-core proteins but contained reverse transcriptase-specific tryptic peptides plus two additional tyrosine-containing tryptic peptides not related to gag or pol gene products [23].

Regulatory relationships of pol

  • To test whether expression of the amphotropic envelope protein was responsible for conferring this serum sensitivity to the RV, env was expressed in the absence of gag and pol in TE671 cells [24].

Analytical, diagnostic and therapeutic context of pol

  • To avoid false-positive results in this assay it is crucial that indicator cell lines are free of endogenous retroviral sequences that could also be amplified with pol-env PCR primers [25].
  • We have used site-directed mutagenesis of cloned Moloney murine leukemia virus (MuLV) DNA to define a function encoded in the 3' region of the viral pol gene and required for efficient integration of viral DNA [26].
  • In vivo ligation experiments involving cotransfection of subclones of pRTM and wild-type murine leukemia virus localized the defect in the clone 23 genome to an approximately 400-base-pair region in the pol gene between the SalI and XhoI sites [27].


  1. Contribution of the gag and pol sequences to the leukemogenicity of Friend murine leukemia virus. Oliff, A., McKinney, M.D., Agranovsky, O. J. Virol. (1985) [Pubmed]
  2. Murine retrovirus-induced spongiform encephalomyelopathy: host and viral factors which determine the length of the incubation period. Czub, M., McAtee, F.J., Portis, J.L. J. Virol. (1992) [Pubmed]
  3. The R-U5-5' leader sequence of neurovirulent wild mouse retrovirus contains an element controlling the incubation period of neurodegenerative disease. Portis, J.L., Perryman, S., McAtee, F.J. J. Virol. (1991) [Pubmed]
  4. A tagged helper-free Friend virus causes clonal erythroblast immortality by specific proviral integration in the cellular genome. Spiro, C., Gliniak, B., Kabat, D. J. Virol. (1988) [Pubmed]
  5. In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an infectious form by the addition of the vesicular stomatitis virus surrogate envelope G protein. Abe, A., Chen, S.T., Miyanohara, A., Friedmann, T. J. Virol. (1998) [Pubmed]
  6. Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Karlsson, H., Bachmann, S., Schröder, J., McArthur, J., Torrey, E.F., Yolken, R.H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  7. Construction and analysis of deletion mutations in the pol gene of Moloney murine leukemia virus: a new viral function required for productive infection. Schwartzberg, P., Colicelli, J., Goff, S.P. Cell (1984) [Pubmed]
  8. Identification of tryptic peptides unique to a 110,000-molecular weight polyprotein encoded by the T-8 isolate of murine leukemia virus. van de Ven, W.J., Reynolds, F.H., Blomberg, J., Stephenson, J.R. J. Exp. Med. (1980) [Pubmed]
  9. Viral reverse transcriptase suppression associated with erythroid differentiation of Friend leukemia cells. Ebert, P.S., Buell, D.N. J. Natl. Cancer Inst. (1977) [Pubmed]
  10. Pseudoknot-dependent read-through of retroviral gag termination codons: importance of sequences in the spacer and loop 2. Wills, N.M., Gesteland, R.F., Atkins, J.F. EMBO J. (1994) [Pubmed]
  11. Synthesis of murine leukemia virus proteins associated with virions assembled in actinomycin D-treated cells: evidence for persistence of viral messenger RNA. Levin, J.G., Rosenak, M.J. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  12. Effects of Poly(1-vinyluracil) and Poly(9-vinyladenine) on viral RNA-directed DNA polymerase. Pitha, J. Cancer Res. (1976) [Pubmed]
  13. Low-molecular- weight Rauscher leukemia virus protein with preferential binding for single-stranded RNA and DNA. Davis, J., Scherer, M., Tsai, W.P., Long, C. J. Virol. (1976) [Pubmed]
  14. A 2.4-kilobase-pair fragment of the Friend murine leukemia virus genome contains the sequences responsible for friend murine leukemia virus-induced erythroleukemia. Oliff, A., Ruscetti, S. J. Virol. (1983) [Pubmed]
  15. At least four non-env factors that reside in the LTR, in the 5'-non-coding region, in gag and in part of pol affect neuropathogenicity of PVC-441 murine leukemia virus (MuLV). Tanaka, A., Saida, K., Andoh, M., Maeda, K., Kai, K. Virus Res. (2000) [Pubmed]
  16. Interruption of env gene expression depending on the length of the SV40 early region used for the polyA signal. Yamakawa, K., Takase-Yoden, S., Watanabe, R. Jpn. J. Infect. Dis. (2005) [Pubmed]
  17. Complete nucleotide sequence of a mouse VL30 retro-element. Adams, S.E., Rathjen, P.D., Stanway, C.A., Fulton, S.M., Malim, M.H., Wilson, W., Ogden, J., King, L., Kingsman, S.M., Kingsman, A.J. Mol. Cell. Biol. (1988) [Pubmed]
  18. Localization of the leukemogenic determinants of SL3-3, an ecotropic, XC-positive murine leukemia virus of AKR mouse origin. Lenz, J., Haseltine, W.A. J. Virol. (1983) [Pubmed]
  19. Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. Ruan, K.S., Lilly, F. Virology (1991) [Pubmed]
  20. A safe packaging line for gene transfer: separating viral genes on two different plasmids. Markowitz, D., Goff, S., Bank, A. J. Virol. (1988) [Pubmed]
  21. Evidence that a downstream pseudoknot is required for translational read-through of the Moloney murine leukemia virus gag stop codon. Wills, N.M., Gesteland, R.F., Atkins, J.F. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  22. Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents. Sharma, S., Murai, F., Miyanohara, A., Friedmann, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  23. Tryptic peptide analysis of gag and gag-pol gene products of Rauscher murine leukemia virus. Kopchick, J.J., Karshin, W.L., Arlinghaus, R.B. J. Virol. (1979) [Pubmed]
  24. Development of amphotropic murine retrovirus vectors resistant to inactivation by human serum. Pensiero, M.N., Wysocki, C.A., Nader, K., Kikuchi, G.E. Hum. Gene Ther. (1996) [Pubmed]
  25. Endogenous murine leukemia virus DNA sequences in murine cell lines: implications for gene therapy safety testing by PCR. Allan, D.S., De Koven, A., Wild, A., Kamel-Reid, S., Dubé, I.D. Leuk. Lymphoma (1996) [Pubmed]
  26. A mutant murine leukemia virus with a single missense codon in pol is defective in a function affecting integration. Donehower, L.A., Varmus, H.E. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  27. Murine leukemia virus mutant with a frameshift in the reverse transcriptase coding region: implications for pol gene structure. Levin, J.G., Hu, S.C., Rein, A., Messer, L.I., Gerwin, B.I. J. Virol. (1984) [Pubmed]
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