Genetic complexity of the human geranylgeranyltransferase I beta-subunit gene: a multigene family of pseudogenes derived from mis-spliced transcripts

Gene
P DhawanK D Mehta

Abstract

Geranylgeranyltransferase I controls the function of a variety of cellular proteins by attaching a geranylgeranyl group to the carboxy-terminus of proteins. The purified enzyme from rat brain is comprised of two polypeptides, a catalytic alpha-subunit (GGTalpha) and a substrate-binding beta-subunit (GGTbeta). The present paper demonstrates the existence of a GGTbeta multigene family in humans by describing the presence and characterization of at least 13 pseudogenes related to this protein. Sequencing of numerous PCR-derived clones, obtained following amplification of human genomic DNA, revealed multiple, distinct but highly related sequences. All clones had a common deletion of 99-bp that conforms to the GT-AG rule of splicing in eukaryotes, and differed from the human GGTbeta cDNA sequence by multiple nucleotide substitutions. PCR amplification from mRNA, however, yielded only the sequence expected for the expressed GGTbeta protein. This apparent paradox was resolved by cloning and sequencing a complete GGTbeta-specific pseudogene. Multiple features of the cloned gene, in particular the absence of introns, presence of flanking direct repeats, and the lack of sequence similarity with the untranscribed region of the gene, indic...Continue Reading

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Citations

Sep 6, 2003·Biological Chemistry·Sebastian Maurer-StrohFrank Eisenhaber
Feb 29, 2000·FEBS Letters·A J MighellA F Markham
Nov 18, 2003·Annual Review of Genetics·Evgeniy S Balakirev, Francisco J Ayala
Mar 20, 1999·General and Comparative Endocrinology·P B Danielson, R M Dores
Apr 19, 2003·Genome Biology·Sebastian Maurer-StrohFrank Eisenhaber

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