IRAS Splice Variants

: The human I1‐imidazoline receptor candidate gene, iras, has previously been cloned and mapped to locus 3p21.1–9 (also known as Nischarin; accession #AC006208). By comparison to a database of expressed sequence tags (ESTs), three alternatively spliced transcripts have been deduced. A map of 21 exons was constructed for the medium‐length transcript (IRAS‐M) containing 5,232 base pairs (bp) and encoding 1,504 amino acids (aas). Introns 13B and 13C are inserted into the two alternative transcripts, forming IRAS‐S and IRAS‐L mRNA (short and long isoforms). Northern blots confirmed the existence of these mRNA isoforms. In most brain regions the order of mRNA abundance was IRAS‐M > IRAS‐L > IRAS‐S mRNA. Although aas 1 through 510 are theoretically identical, truncated proteins could be derived from IRAS‐S (2,678 bp transcript yields 515 aas) and IRAS‐L (9,457 bp transcript yields 583 aas). Because exon‐16 of the iras gene has been proposed to encode the functional domains of imidazoline and a‐5 integrin binding, only IRAS‐M is expected to possess I1 receptor properties. Subtype‐selective cDNA expression constructs were therefore generated and used to transfect CHO cells. High‐affinity I1 binding was endowed by IRAS‐M and IRAS‐L, but not by IRAS‐S transfection.