In silico Validation of Expressed Sequence Tags for Alternate Splice Variants of Human myo-inositol Oxygenase Gene.

Abstract

Myo-Inositol oxygenase (MIOX) is an enzyme that catabolizes myo-inositol in humans. There is increased MIOX expression and increased MIOX activity in renal tubular cells in diabetic nephropathy. One potential mechanism of increased expression and activity of MIOX is the production of one or more highly stable alternative splice isoform of MIOX transcript. Based on the evidence gathered from the expressed sequence tags (ESTs) associated with MIOX protein sequence, we report that retention of intron 9 in MIOX transcript is a valid alternative splice mechanism. This alternative splice isoform is predicted to have higher stability than the canonical MIOX transcript. Higher stability of the alternative splice variant leads to increased production of MIOX protein isoform with retained structural and potentially, functional features of canonical MIOX protein. Production of this MIOX transcript isoform could be the mechanism of increased expression and activity of MIOX in renal tissues affected by diabetes mellitus. Alteration of the splice mechanism could be a new therapeutic target in prevention and treatment of complications of diabetes mellitus.