Truncation of Exon 1 from the C-myc Gene Results in Prolonged C-myc MRNa Stability

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1985 Dec 30

PMID 4092694

Citations 57

Authors

P H Rabbitts

A Forster

M A Stinson

T H Rabbitts

Affiliations

Soon will be listed here.

Abstract

The human c-myc gene consists of three exons transcribed from two distinct promoters and the function of the first, noncoding exon is unknown. In COLO 320 cells, there co-exist normal and truncated (i.e., lacking exon 1) c-myc genes, both of which are transcribed. Studies on the turnover of c-myc mRNA show that the normal mRNA has an in vivo half-life of approximately 30 min which is approximately similar to the turnover time of the mRNA in lymphoblastoid cells. However, the truncated mRNA was found to be substantially more stable. This observation was also made with a Burkitt's lymphoma cell line which has a translocated, truncated c-myc gene. Therefore truncation of the c-myc gene can cause the mRNA to be more stable than the full size product suggesting that this can be a crucial factor in the activation of the c-myc oncogene, by exon 1 loss, in chromosomal translocation. The results also suggest a role for exon 1 in the c-myc mRNA degradative mechanism.

Citing Articles

Tracing MYC Expression for Small Molecule Discovery.

Steinberger J, Robert F, Halle M, Williams D, Cencic R, Sawhney N Cell Chem Biol. 2019; 26(5):699-710.e6.

PMID: 30880156 PMC: 6525070. DOI: 10.1016/j.chembiol.2019.02.007.

Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner.

Jacobs P, Cao L, Samon J, Kane C, Hedblom E, Bowcock A PLoS One. 2013; 8(7):e69083.

PMID: 23874874 PMC: 3715461. DOI: 10.1371/journal.pone.0069083.

Small interfering RNAs against the TAR RNA binding protein, TRBP, a Dicer cofactor, inhibit human immunodeficiency virus type 1 long terminal repeat expression and viral production.

Christensen H, Daher A, Soye K, Frankel L, Alexander M, Laine S J Virol. 2007; 81(10):5121-31.

PMID: 17360756 PMC: 1900231. DOI: 10.1128/JVI.01511-06.

Negative control of the Myc protein by the stress-responsive kinase Pak2.

Huang Z, Traugh J, Bishop J Mol Cell Biol. 2004; 24(4):1582-94.

PMID: 14749374 PMC: 344192. DOI: 10.1128/MCB.24.4.1582-1594.2004.

Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR.

Akool E, Kleinert H, Hamada F, Abdelwahab M, Forstermann U, Pfeilschifter J Mol Cell Biol. 2003; 23(14):4901-16.

PMID: 12832476 PMC: 162218. DOI: 10.1128/MCB.23.14.4901-4916.2003.

References

Hamlyn P, Rabbitts T . Translocation joins c-myc and immunoglobulin gamma 1 genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene. Nature. 1983; 304(5922):135-9. DOI: 10.1038/304135a0. View

Leder P, Battey J, Lenoir G, Moulding C, Murphy W, Potter H . Translocations among antibody genes in human cancer. Science. 1983; 222(4625):765-71. DOI: 10.1126/science.6356357. View

Cory S, Gerondakis S, Adams J . Interchromosomal recombination of the cellular oncogene c-myc with the immunoglobulin heavy chain locus in murine plasmacytomas is a reciprocal exchange. EMBO J. 1983; 2(5):697-703. PMC: 555172. DOI: 10.1002/j.1460-2075.1983.tb01487.x. View

Little C, Nau M, Carney D, Gazdar A, Minna J . Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983; 306(5939):194-6. DOI: 10.1038/306194a0. View

Croce C, Thierfelder W, Erikson J, Nishikura K, Finan J, Lenoir G . Transcriptional activation of an unrearranged and untranslocated c-myc oncogene by translocation of a C lambda locus in Burkitt. Proc Natl Acad Sci U S A. 1983; 80(22):6922-6. PMC: 390098. DOI: 10.1073/pnas.80.22.6922. View

Dunnick W, Shell B, Dery C . DNA sequences near the site of reciprocal recombination between a c-myc oncogene and an immunoglobulin switch region. Proc Natl Acad Sci U S A. 1983; 80(23):7269-73. PMC: 390036. DOI: 10.1073/pnas.80.23.7269. View

Kelly K, Cochran B, Stiles C, Leder P . Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983; 35(3 Pt 2):603-10. DOI: 10.1016/0092-8674(83)90092-2. View

Rabbitts T, Hamlyn P, Baer R . Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma. Nature. 1983; 306(5945):760-5. DOI: 10.1038/306760a0. View

TAUB R, Moulding C, Battey J, Murphy W, Vasicek T, Lenoir G . Activation and somatic mutation of the translocated c-myc gene in burkitt lymphoma cells. Cell. 1984; 36(2):339-48. DOI: 10.1016/0092-8674(84)90227-7. View

10.

Hayday A, Gillies S, Saito H, Wood C, Wiman K, Hayward W . Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus. Nature. 1984; 307(5949):334-40. DOI: 10.1038/307334a0. View

11.

Bernard O, Cory S, Gerondakis S, Webb E, Adams J . Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. EMBO J. 1983; 2(12):2375-83. PMC: 555460. DOI: 10.1002/j.1460-2075.1983.tb01749.x. View

12.

Hollis G, Mitchell K, Battey J, Potter H, TAUB R, Lenoir G . A variant translocation places the lambda immunoglobulin genes 3' to the c-myc oncogene in Burkitt's lymphoma. Nature. 1984; 307(5953):752-5. DOI: 10.1038/307752a0. View

13.

Davis M, Malcolm S, Rabbitts T . Chromosome translocation can occur on either side of the c-myc oncogene in Burkitt lymphoma cells. Nature. 1984; 308(5956):286-8. DOI: 10.1038/308286a0. View

14.

Saito H, Hayday A, Wiman K, Hayward W, Tonegawa S . Activation of the c-myc gene by translocation: a model for translational control. Proc Natl Acad Sci U S A. 1983; 80(24):7476-80. PMC: 389974. DOI: 10.1073/pnas.80.24.7476. View

15.

Erikson J, Nishikura K, Finan J, Emanuel B, Lenoir G, Nowell P . Translocation of an immunoglobulin kappa locus to a region 3' of an unrearranged c-myc oncogene enhances c-myc transcription. Proc Natl Acad Sci U S A. 1983; 80(24):7581-5. PMC: 534384. DOI: 10.1073/pnas.80.24.7581. View

16.

Tuan D, LONDON I . Mapping of DNase I-hypersensitive sites in the upstream DNA of human embryonic epsilon-globin gene in K562 leukemia cells. Proc Natl Acad Sci U S A. 1984; 81(9):2718-22. PMC: 345141. DOI: 10.1073/pnas.81.9.2718. View

17.

Siebenlist U, Hennighausen L, Battey J, Leder P . Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in Burkitt lymphoma. Cell. 1984; 37(2):381-91. DOI: 10.1016/0092-8674(84)90368-4. View

18.

Denhardt D . A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966; 23(5):641-6. DOI: 10.1016/0006-291x(66)90447-5. View

19.

Southern E . Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975; 98(3):503-17. DOI: 10.1016/s0022-2836(75)80083-0. View

20.

Favaloro J, Treisman R, Kamen R . Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980; 65(1):718-49. DOI: 10.1016/s0076-6879(80)65070-8. View