TRANSCRIPTIONAL REPRESSION MECHANISM OF TROCARIN D, A SNAKE VENOM PROTHROMBIN ACTIVATOR FROM TROPIDECHIS CARINATUS

Abstract

Trocarin D (TroD), a venom prothrombin activator from Tropidechis carinatus shares similar structure and function with blood coagulation factor Xa (TrFXa). Their distinct physiological roles are due to distinct expression patterns. The genes of TroD and TrFX are highly similar, except for promoter and intron 1. The promoter insertion in TroD accounts for the elevated but not venom gland-specific expression. We examined the roles of three insertions and two deletions in intron 1 of TroD in the regulation of expression, and found a 209-bp region within the second insertion silences expression. We identified five AG-rich motifs in this region. All except the 5th motif are important for silencing function via recruitment of YY1, Sp3 and HMGB2. Similar AG-rich motif clusters are found in other toxin genes but not in their physiological counterparts. Thus, AG-rich motifs contribute to regulation of expression of TroD, and probably other toxin genes.