Abstract
The c-abl gene encodes a protein tyrosine kinase and is transcribed from at least two promoters giving rise to transcripts of two size classes of approximately 5 and 6 kb in length. These mRNAs only differ in their most 5' exon and encode proteins of similar size but with different N-termini. In the mouse testis an additional abundant c-abl mRNA of 4 kb is detected. This mRNA was shown to be expressed in the haploid male germ cells of the adult mouse. Here we describe the cloning and molecular characterization of a cDNA representing the testis specific c-abl transcript. We show that the 4 kb c-abl mRNA arises from alternative polyadenylation of an RNA transcribed from the same promoter as the 5 kb mRNA. The site of polyadenylation is unusual in this shorter transcript as it is not preceded by the highly conserved hexanucleotide AAUAAA. The use of this polyadenylation site removes 1.2 kb of 3' sequences present in the somatic c-abl mRNAs, but does not affect the main open reading frame of the transcript. Using in situ hybridization on whole testis sections it is shown that the 4 kb c-abl mRNA is most abundant in the elongating spermatids.
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- Akam M. E. The location of Ultrabithorax transcripts in Drosophila tissue sections. EMBO J. 1983;2(11):2075–2084. doi: 10.1002/j.1460-2075.1983.tb01703.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Amara S. G., Evans R. M., Rosenfeld M. G. Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites. Mol Cell Biol. 1984 Oct;4(10):2151–2160. doi: 10.1128/mcb.4.10.2151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ben-Neriah Y., Bernards A., Paskind M., Daley G. Q., Baltimore D. Alternative 5' exons in c-abl mRNA. Cell. 1986 Feb 28;44(4):577–586. doi: 10.1016/0092-8674(86)90267-9. [DOI] [PubMed] [Google Scholar]
- Berget S. M. Are U4 small nuclear ribonucleoproteins involved in polyadenylation? Nature. 1984 May 10;309(5964):179–182. doi: 10.1038/309179a0. [DOI] [PubMed] [Google Scholar]
- Bernards A., Rubin C. M., Westbrook C. A., Paskind M., Baltimore D. The first intron in the human c-abl gene is at least 200 kilobases long and is a target for translocations in chronic myelogenous leukemia. Mol Cell Biol. 1987 Sep;7(9):3231–3236. doi: 10.1128/mcb.7.9.3231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
- Collins S. J., Kubonishi I., Miyoshi I., Groudine M. T. Altered transcription of the c-abl oncogene in K-562 and other chronic myelogenous leukemia cells. Science. 1984 Jul 6;225(4657):72–74. doi: 10.1126/science.6587568. [DOI] [PubMed] [Google Scholar]
- Dani C., Blanchard J. M., Piechaczyk M., El Sabouty S., Marty L., Jeanteur P. Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046–7050. doi: 10.1073/pnas.81.22.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Early P., Rogers J., Davis M., Calame K., Bond M., Wall R., Hood L. Two mRNAs can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways. Cell. 1980 Jun;20(2):313–319. doi: 10.1016/0092-8674(80)90617-0. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Gil A., Proudfoot N. J. Position-dependent sequence elements downstream of AAUAAA are required for efficient rabbit beta-globin mRNA 3' end formation. Cell. 1987 May 8;49(3):399–406. doi: 10.1016/0092-8674(87)90292-3. [DOI] [PubMed] [Google Scholar]
- Goddard J. M., Weiland J. J., Capecchi M. R. Isolation and characterization of Caenorhabditis elegans DNA sequences homologous to the v-abl oncogene. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2172–2176. doi: 10.1073/pnas.83.7.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goff S. P., Gilboa E., Witte O. N., Baltimore D. Structure of the Abelson murine leukemia virus genome and the homologous cellular gene: studies with cloned viral DNA. Cell. 1980 Dec;22(3):777–785. doi: 10.1016/0092-8674(80)90554-1. [DOI] [PubMed] [Google Scholar]
- Grootegoed J. A., Jansen R., van der Molen H. J. Effect of glucose on ATP dephosphorylation in rat spermatids. J Reprod Fertil. 1986 May;77(1):99–107. doi: 10.1530/jrf.0.0770099. [DOI] [PubMed] [Google Scholar]
- Hafen E., Levine M., Garber R. L., Gehring W. J. An improved in situ hybridization method for the detection of cellular RNAs in Drosophila tissue sections and its application for localizing transcripts of the homeotic Antennapedia gene complex. EMBO J. 1983;2(4):617–623. doi: 10.1002/j.1460-2075.1983.tb01472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufman R. J., Sharp P. A. Growth-dependent expression of dihydrofolate reductase mRNA from modular cDNA genes. Mol Cell Biol. 1983 Sep;3(9):1598–1608. doi: 10.1128/mcb.3.9.1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kessler M. M., Beckendorf R. C., Westhafer M. A., Nordstrom J. L. Requirement of A-A-U-A-A-A and adjacent downstream sequences for SV40 early polyadenylation. Nucleic Acids Res. 1986 Jun 25;14(12):4939–4952. doi: 10.1093/nar/14.12.4939. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Konopka J. B., Witte O. N. Activation of the abl oncogene in murine and human leukemias. Biochim Biophys Acta. 1985 Nov 12;823(1):1–17. doi: 10.1016/0304-419x(85)90012-5. [DOI] [PubMed] [Google Scholar]
- Le Bouc Y., Dreyer D., Jaeger F., Binoux M., Sondermeyer P. Complete characterization of the human IGF-I nucleotide sequence isolated from a newly constructed adult liver cDNA library. FEBS Lett. 1986 Feb 3;196(1):108–112. doi: 10.1016/0014-5793(86)80223-x. [DOI] [PubMed] [Google Scholar]
- LeMeur M. A., Galliot B., Gerlinger P. Termination of the ovalbumin gene transcription. EMBO J. 1984 Dec 1;3(12):2779–2786. doi: 10.1002/j.1460-2075.1984.tb02209.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linial M., Gunderson N., Groudine M. Enhanced transcription of c-myc in bursal lymphoma cells requires continuous protein synthesis. Science. 1985 Dec 6;230(4730):1126–1132. doi: 10.1126/science.2999973. [DOI] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- McDevitt M. A., Hart R. P., Wong W. W., Nevins J. R. Sequences capable of restoring poly(A) site function define two distinct downstream elements. EMBO J. 1986 Nov;5(11):2907–2913. doi: 10.1002/j.1460-2075.1986.tb04586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McLauchlan J., Gaffney D., Whitton J. L., Clements J. B. The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3' termini. Nucleic Acids Res. 1985 Feb 25;13(4):1347–1368. doi: 10.1093/nar/13.4.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller R., Slamon D. J., Tremblay J. M., Cline M. J., Verma I. M. Differential expression of cellular oncogenes during pre- and postnatal development of the mouse. Nature. 1982 Oct 14;299(5884):640–644. doi: 10.1038/299640a0. [DOI] [PubMed] [Google Scholar]
- Orkin S. H., Cheng T. C., Antonarakis S. E., Kazazian H. H., Jr Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. EMBO J. 1985 Feb;4(2):453–456. doi: 10.1002/j.1460-2075.1985.tb03650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Owen D., Kühn L. C. Noncoding 3' sequences of the transferrin receptor gene are required for mRNA regulation by iron. EMBO J. 1987 May;6(5):1287–1293. doi: 10.1002/j.1460-2075.1987.tb02366.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
- Ponzetto C., Wolgemuth D. J. Haploid expression of a unique c-abl transcript in the mouse male germ line. Mol Cell Biol. 1985 Jul;5(7):1791–1794. doi: 10.1128/mcb.5.7.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
- Reddy E. P., Smith M. J., Srinivasan A. Nucleotide sequence of Abelson murine leukemia virus genome: structural similarity of its transforming gene product to other onc gene products with tyrosine-specific kinase activity. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3623–3627. doi: 10.1073/pnas.80.12.3623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selten G., Cuypers H. T., Boelens W., Robanus-Maandag E., Verbeek J., Domen J., van Beveren C., Berns A. The primary structure of the putative oncogene pim-1 shows extensive homology with protein kinases. Cell. 1986 Aug 15;46(4):603–611. doi: 10.1016/0092-8674(86)90886-x. [DOI] [PubMed] [Google Scholar]
- Setzer D. R., McGrogan M., Nunberg J. H., Schimke R. T. Size heterogeneity in the 3' end of dihydrofolate reductase messenger RNAs in mouse cells. Cell. 1980 Nov;22(2 Pt 2):361–370. doi: 10.1016/0092-8674(80)90346-3. [DOI] [PubMed] [Google Scholar]
- Setzer D. R., McGrogan M., Schimke R. T. Nucleotide sequence surrounding multiple polyadenylation sites in the mouse dihydrofolate reductase gene. J Biol Chem. 1982 May 10;257(9):5143–5147. [PubMed] [Google Scholar]
- Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
- Shilo B. Z., Weinberg R. A. DNA sequences homologous to vertebrate oncogenes are conserved in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6789–6792. doi: 10.1073/pnas.78.11.6789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shtivelman E., Lifshitz B., Gale R. P., Roe B. A., Canaani E. Alternative splicing of RNAs transcribed from the human abl gene and from the bcr-abl fused gene. Cell. 1986 Oct 24;47(2):277–284. doi: 10.1016/0092-8674(86)90450-2. [DOI] [PubMed] [Google Scholar]
- Telford J., Burckhardt J., Butler B., Pirrotta V. Alternative processing and developmental control of the transcripts of the Drosophila abl oncogene homologue. EMBO J. 1985 Oct;4(10):2609–2615. doi: 10.1002/j.1460-2075.1985.tb03978.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tosi M., Young R. A., Hagenbüchle O., Schibler U. Multiple polyadenylation sites in a mouse alpha-amylase gene. Nucleic Acids Res. 1981 May 25;9(10):2313–2323. doi: 10.1093/nar/9.10.2313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang J. Y., Baltimore D. Cellular RNA homologous to the Abelson murine leukemia virus transforming gene: expression and relationship to the viral sequence. Mol Cell Biol. 1983 May;3(5):773–779. doi: 10.1128/mcb.3.5.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang J. Y., Ledley F., Goff S., Lee R., Groner Y., Baltimore D. The mouse c-abl locus: molecular cloning and characterization. Cell. 1984 Feb;36(2):349–356. doi: 10.1016/0092-8674(84)90228-9. [DOI] [PubMed] [Google Scholar]
- Wickens M., Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. doi: 10.1126/science.6208611. [DOI] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
- Zehner Z. E., Paterson B. M. Characterization of the chicken vimentin gene: single copy gene producing multiple mRNAs. Proc Natl Acad Sci U S A. 1983 Feb;80(4):911–915. doi: 10.1073/pnas.80.4.911. [DOI] [PMC free article] [PubMed] [Google Scholar]