Abstract
Two isoforms of the protein kinase A catalytic subunit, Cα and Cβ, have previously been described in the mouse. We now report the cloning and characterization of a novel C-related sequence, Cx, from a murine genomic library. Cx is 89.8% identical to part of the Cα coding region, but lacks all of the introns present in this gene, suggesting that is arose via retroposition. The existence of several frameshift mutations, premature termination codons, and missense mutations at critical sites confirms that it is a pseudogene. Furthermore, we are unable to detect any expression. Homology with functional protein kinase genes commences exactly at the first intron splice junction in Cα, downstream of the expected translational start codon. Cx is also truncated at its 3′ end by the interposition of two distinct, contiguous LINE-1 elements. By fluorescence in situ hybridization, we demonstrate that Cx is located on the X Chromosome (Chr), at band F3. This is displaced from its functional homologs, Cα and Cβ, which we map to mouse Chrs 8 (band C3) and 3 (band H3), respectively.
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References
Ashworth, A., Skene, B., Swift, S., Lovell-Badge, R. (1990). Zfa is an expressed retroposon derived from an alternative transcript of the Zfx gene. EMBO J. 9, 1529–1534.
Battey, J., Max, E., McBride, W., Swan, D., Leder, P. (1982). A processed human immunoglobulin ɛ gene has moved to chromosome 9. Proc. Natl. Acad. Sci. 79, 5956–5960.
Beebe, S., Oyen, O., Sandberg, M., Froysa, A., Hansson, V., Jahnsen, T. (1990) Molecular cloning of a tissue-specific protein kinase (Cγ) from human testis—representing a third isoform of the catalytic subunit of cAMP-dependent protein kinase. Mol. Endocrinol. 4, 465–475.
Chrivia, J., Uhler, M., McKnight, G. (1988). Characterization of genomic clones coding for the Cα and Cβ subunits of mouse cAMP-dependent protein kinase. J. Biol. Chem. 263, 5739–5744.
Dahl, H-H., Brown, R., Hutchison, W., Maragos, C., Brown, G. (1990). A testis-specific form of the human pyruvate dehydrogenase E1α subunit is coded for by an intronless gene on chromosome 4. Genomics 8, 225–232.
Edelhoff, S., Ayer, D., Zervos, A., Steingrimess, E., Jenkins, N., Copeland, N., Eisenman, R., Brent, R., Disteche, C. (1994). Mapping of two genes encoding members of a distinct subfamily of MAX interacting proteins: MAD to human chromosome 2 and mouse chromosome 6, and MXI1 to human chromosome 10 and mouse chromosome 19. Oncogene 9, 665–668.
Fourel, G., Trepo, C., Bougueleret, L., Henglein, B., Ponzetto, A., Tiollais, P., Buendia, M-A. (1990). Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours. Nature 347, 294–298.
Green, M. (1989). Catalogue of mutant genes and polymorphic loci. In Genetic Variants and Strains of the Laboratory Mouse, M. Lyon, A. Searle, eds. (New York: Oxford University Press), pp. 12–403.
Hanks, S., Quinn, A., Hunter, T. (1988). The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241, 42–52.
Hollis, G., Hieter, P., McBride, O., Swan, D., Leder, P. (1982). Processed genes: a dispersed human immunoglobulin gene bearing evidence of RNA-type processing. Nature 296, 321–325.
Jacq, C., Miller, J., Brownlee, G. (1977). A pseudogene structure in 5S DNA of Xenopus laevis. Cell 12, 109–120.
Knighton, D., Zheng, J., Ten Eyck, L., Xuong, N., Taylor, S., Sowadski, J. (1991). Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science 253, 414–420.
Kricker, M., Drake, J., Radman, M. (1992). Duplication-targeted DNA methylation and mutagenesis in the evolution of eukaryotic chromosomes. Proc. Natl. Acad. Sci. USA 89, 1075–1079.
Maeda, N., Wu, C., Bliska, J., Reneke, J. (1988). Molecular evolution of intergenic DNA in higher primates: pattern of DNA changes, molecular clock and evolution of repetitive sequences. Mol. Biol. Evol. 5, 1–20.
McCarrey, J., Thomas, K. (1987). Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature 326, 501–505.
McKnight, G. (1991). Cyclic AMP second messenger systems. Curr. Opin. Cell Biol. 3, 213–217.
Orellana, S., McKnight, G. (1990). The S49 kin- cell line transcribes and translates a functional mRNA coding for the catalytic subunit of cAMP-dependent protein kinase. J. Biol. Chem. 265, 3048–3053.
Saiki, R., Gelfand, D., Stoffel, S., Scarf, S., Higuchi, R., Horn, G., Mullis, K., Erlich, H. (1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239, 487–491.
Samuelson, L., Wiebauer, K., Snow, C., Meisler, M. (1990). Retroviral and pseudogene insertion sites reveal the lineage of human salivery and pancreatic amylase genes from a single gene during primate evolution. Mol. Cell. Biol. 10, 2513–2520.
Scarpulla, R. (1985). Association of a truncated cytochrome c processed pseudogene with a similarly truncated member from a long interspersed repeat family of rat. Nucleic Acids Res. 13, 763–775.
Shimada, T., Chen, M-J., Nienhuis, A. (1984). A human dihydrofolate reductase intronless pseudogene with an Alu repetitive sequence: multiple DNA insertions at a single chromosomal site. Gene 31, 1–8.
Simard, J., Berube, D., Sandberg, M., Grzeschik, K-H., Gagne, R., Hansson, V., Jahnsen, T. (1992) Assignment of the gene encoding the catalytic subunit Cβ of cAMP-dependent protein kinase A to the p36 band on chromosome 1. Hum. Genet. 88, 653–657.
Soares, M., Schon, E., Henderson, A., Karathanasis, S., Cate, R., Zeitlin, S., Chirgwin, J., Efstratiadis, A. (1985). RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon. Mol. Cell. Biol. 5, 2090–2103.
Solberg, R., Sandberg, M., Spurkland, A., Jahnsen, T. (1993). Isolation and characterization of a human pseudogene for the regulatory subunit RIα of cAMP-dependent protein kinases and its sublocalization on chromosome 1. Genomics 15, 591–597.
Tokunaga, K., Yoda, K., Sakiyama, S. (1985). Structure of a processed gene of mouse cytoplasmic γ-actin transposed into a BAM5 sequence: insertion has created 13 base-pair direct repeats. Nucleic Acids Res. 13, 3031–3042.
Uhler, M., Chrivia, J., McKnight, G. (1986). Evidence for a second isoform of the catalytic subunit of cAMP-dependent protein kinase. J. Biol. Chem. 261, 15360–15363.
Vanin, E. (1985). Processed pseudogenes: characteristics and evolution. Annu. Rev. Genet. 19, 253–272.
Watson, J., Sutcliffe, J. (1987). Primate brain-specific cytoplasmic transcript of the Alu repeat family. Mol. Cell. Biol. 7, 3324–3327.
Weiner, A., Deininger, P., Efstratiadis, A. (1986). Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu. Rev. Biochem. 55, 631–661.
Zakut-Houri, R., Oren, M., Bienz, B., Lavie, V., Hazum, S., Givol, D. (1983). A single gene and a pseudogene for the cellular tumour antigen p53. Nature 306, 594–597.
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Cummings, D.E., Edelhoff, S., Disteche, C.M. et al. Cloning of a mouse protein kinase A catalytic subunit pseudogene and chromosomal mapping of C subunit isoforms. Mammalian Genome 5, 701–706 (1994). https://doi.org/10.1007/BF00426076
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DOI: https://doi.org/10.1007/BF00426076