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Nucleic Acids Research, 1992, Vol. 20, No. 16 4263-4267
© 1992


MOLECULAR BIOLOGY

Aberrant splicing of Gs{alpha} transcript in transformed human astroglial and gliobastoma cell lines

Iqbal Unnisa Ali, William Reinhold, Carolina Salvador and Salvatore Aguanno

Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Insitutes of Health Bethesda, MD 20892, USA

Received May 5, 1992. Accepted July 23, 1992.

Alpha subunits of G proteins, which play a vital role in signal transductlon, display considerable structural and functional diversity. Point mutations in two forms of alpha subunits, Gs{alpha} and Gi2{alpha}, impairing their GTPase activity, have been detected in endocrine disorders. We report here the presence of truncated Gs{alpha} transcripts in a human glioblastoma cell line, HS683, and in an SV40-transformed human astroglial cell line, SVG. These transcripts were detected by polymerase chain reaction (PCR) amplification of cDNAs from the cell lines. The truncated Gsa transcripts, with deletions in the central region of the molecule, seem to have originated due to aberrant splicing within exonlc sequences, which did not conform to the consensus GT/AG splice signals. The presence of a smaller size protein of mol.wt. around 25,000 kd in the SVG and HS683 cell lines, detected by antibodies specific for the C-termlnal region of the Gs{alpha} subunit, seems to be consistent with the presence of truncated Gs{alpha} transcripts in these cell lines. These aberrantly spliced transcripts, if translated, could synthesize potentially oncogenic Gs{alpha} subunits deficient in GTPase activity. Whether such molecules, with sometimes relatively large deletions, retain some aspects of their function and are biologically significant remains to be seen.


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