Structure characterization of human RalGDS gene, and the identification ofits novel variant

RalGDS is a guanine nucleotide dissociation stimulator for Ral, which is a member of the Ras GTPase superfamily that regulates cellular proliferation, differentiation and transformation by mediating multiple signal transducti on pathways. RalGDS can specifically promote the conversion from an inactiv e GDP-bound state to an active GTP-bound state for Ral. The cDNA of human R alGDS has been cloned recently. In this paper, by comparison between the ge ne's genomic and cDNA seqence, we determined the structure of the gene, whi ch showed that the reported human RalGDS transcribed from 18 exons. Further more, a novel variant of RalGDS that codes for a protein with a different N -terminus was cloned and identified. Northern hybridization revealed that t he novel transcript was of 6.0 kb in length while the transcript previously reported is of 4.0 kb. Both transcripts were ubiquitously expressed in hum an adult tissues examined, albeit with different amounts. In addition, this novel transcript was proved to be caused by employment of a new exon, desi gnated as exon 1a, instead of the one, designated as exon 1b, in the report ed cDNA. Thus, the RalGDS gene consists of at least 19 exons and spanned a 44 kb region. The length between exon 1a and exon 2 was 33 kb, while the le ngth between exon 1b and exon 2 was 8.8 kb.