Signaling mechanisms underlying the induction of the pre-pancreatic tissue within the endoderm remain poorly understood. Through an expression cloning strategy, we have identified a previously uncharacterized pancreatic factor that we named Shirin. Interestingly, the non-coding RNA regulatory sequence (3'UTR) of Shirin is sufficient to induce insulin expression in Xenopus embryos. Biochemical studies demonstrate that this RNA sequence is able to bind directly to a trans-acting factor, VgIRBP, which was previously shown to be involved in the localization of endodermal determinant factors. Loss-of-function analysis indicates that VgIRBP is required for establishment of pancreatic fate within the endoderm, suggesting a synergism between VgIRBP and Shirin in the embryo. This study argues for a central role of post-transcriptional mechanisms in establishing pancreatic fate, where a 3'UTR may recruit factors necessary for pancreatic development.. and highlights an unknown embryological activity of VgIRBP. (c) 2006 Elsevier Inc. All rights reserved.