Cloning and characterization of a LASS1-GDF1 transcript in rat cerebral cortex: Conservation of a bicistronic structure

LASS1 is the mammalian homologue of yeast longevity-assurance gene 1 ( LAG1) which is differentially expressed during the yeast replicative life span and was shown to play a role in determining yeast longevity. Growth/differentiation factor 1 ( GDF1) is a transforming growth factor-beta family member that was originally isolated from an mouse embryo cDNA library. GDF1 is expressed specifically in the nervous system and functions in left-right patterning of the mouse embryo. To explore the potential role of LASS1 in rat neuron aging, northern blot analysis for LASS1 mRNA was performed and detected a 2.7 kb transcript in adult rat cerebral cortex. Cloning and sequence analysis revealed that this transcript contains two nonoverlapping open reading frames ( ORFs), LASS1 and GDF1, which are quite different to the predicted sequences in GenBank ( accession number XM_224734 and XM_224733). The alignment with the rat genome database revealed this transcript matches the sequence of rat chromosome 16 genomic contig ( GenBank accession number NW_047470) between nucleotide positions 1935060th and 1919439th, which contains eight exons and seven introns. Multiple sequence analysis revealed high conservation of the two ORFs. The phylogenetic analysis showed very close evolutionary relationship among rat, mouse and human. It raises the possibility that this mRNA may give rise to two different proteins and the conserved bicistronic structure might be of unknown significance.