Departmentof Life Science, National Chung Cheng University, Chia-Yi, Taiwan.
DNA Cell Biol. 2012 Jul;31(7):1245-51. doi: 10.1089/dna.2012.1619. Epub 2012 Feb 28.
The development of the pancreas is a complicated process that is regulated on several levels. Pancreas transcription factor 1, alpha subunit (Ptf1a), also known as p48, is a pancreas-specific basic helix-loop-helix transcription factor that is critical for both exocrine pancreas development and maintenance of acinar cell differentiation. Based on a differential screening assay, we identified Rbms3, a gene encoding a glycine-rich RNA-binding protein, to be specifically expressed in the neural tube and the pancreatic rudiment of e10.5 embryos. The presence of Rbms3 in the early developing pancreas suggests that specific post-transcriptional regulation mechanisms play an important role in controlling pancreas development. In this study, we show that Rbms3 binds to the 3'UTR of Ptf1a mRNA, but not the 3'UTR of Pdx1, which is another pancreatic transcription factor. The ectopic expression of Rbms3 stimulates the translation of a reporter gene carrying the Ptf1a 3'UTR. In addition, when Rbms3 expression is suppressed in the AR42J-B13 pancreatic exocrine cell line, the expression of Ptf1a is also down-regulated. These results suggest that binding of Rbms3 to the 3'UTR of Ptf1a regulates the production of the Ptf1a protein and, thereby, indirectly regulates the expression of the Ptf1a downstream target genes.
胰腺的发育是一个复杂的过程，受到多个层面的调控。胰腺转录因子 1，α亚基（Ptf1a），也称为 p48，是一种胰腺特异性的基本螺旋-环-螺旋转录因子，对于外分泌腺的发育和维持腺泡细胞分化至关重要。基于差异筛选分析，我们鉴定出 Rbms3 是一种编码富含甘氨酸的 RNA 结合蛋白的基因，其在 e10.5 胚胎的神经管和胰腺原基中特异性表达。Rbms3 存在于早期发育的胰腺中，这表明特定的转录后调控机制在控制胰腺发育中发挥着重要作用。在这项研究中，我们表明 Rbms3 结合到 Ptf1a mRNA 的 3'UTR，但不结合另一种胰腺转录因子 Pdx1 的 3'UTR。Rbms3 的异位表达刺激携带 Ptf1a 3'UTR 的报告基因的翻译。此外，当 Rbms3 在 AR42J-B13 胰腺外分泌细胞系中被抑制表达时，Ptf1a 的表达也下调。这些结果表明，Rbms3 与 Ptf1a 的 3'UTR 结合调节 Ptf1a 蛋白的产生，从而间接调节 Ptf1a 下游靶基因的表达。
