The RNA-binding protein, Vg1RBP, is required for pancreatic fate specification

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 sequen...

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Bibliographic Details
Published in:Developmental biology 2006-04, Vol.292 (2), p.442-456
Main Authors: Spagnoli, Francesca M., Brivanlou, Ali H.
Format: Article
Language:English
Subjects:
3' Untranslated Regions
3′UTR
Animals
Base Sequence
Biomarkers - analysis
Blotting, Western
Cross-Linking Reagents - pharmacology
DNA, Complementary - chemistry
Embryo, Nonmammalian
Glycoproteins - genetics
Glycoproteins - physiology
GTPase-Activating Proteins - chemistry
GTPase-Activating Proteins - genetics
In Situ Hybridization
Insulin
Insulin - metabolism
Models, Biological
Molecular Sequence Data
Oligonucleotides, Antisense - pharmacology
Pancreas
Pancreas - embryology
Point Mutation
Precipitin Tests
Reverse Transcriptase Polymerase Chain Reaction
RNA-Binding Proteins - physiology
Shirin
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - physiology
Vg1RBP
Xenopus - embryology
Xenopus Proteins - chemistry
Xenopus Proteins - genetics
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Summary: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, Vg1RBP, which was previously shown to be involved in the localization of endodermal determinant factors. Loss-of-function analysis indicates that Vg1RBP is required for establishment of pancreatic fate within the endoderm, suggesting a synergism between Vg1RBP 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 Vg1RBP.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2006.01.022