Developmental regulation of a proinsulin messenger RNA generated by intron retention
Developmental regulation of a proinsulin messenger RNA generated by intron retention
复制标题
DOI：
10.1038/sj.embor.7400539
复制
发表时间：
2005-12-01
期刊：
影响因子：
7.7
通讯作者：
Hernández-Sánchez, C
中科院分区：
文献类型：
--
作者：
Mansilla, A;López-Sánchez, C;Hernández-Sánchez, C
胰岛素原基因表达调控和功能在早期胚胎发育过程中显着不同，在出生后的生物体。胚胎胰岛素原蛋白质含量下降，从原肠胚到神经形成的整体胰岛素原信使RNA的增加。这是由于50非翻译区中内含子1保留产生的胰岛素原mRNA变体水平增加。包含内含子1抑制胰岛素原翻译几乎完全不影响核输出或细胞质衰变。新的胰岛素原mRNA亚型的表达是发育调节和组织特异性。从原肠胚形成到器官形成，内含子保留的比例逐渐增加，在心管和体前区最高，在胰腺中未检测到。值得注意的是，胰岛素原添加诱导心脏标志物基因在胚胎早期阶段的表达时，表达的抑制活性的转录。我们建议，受管制的非生产性剪接和翻译是一种机制，调节胰岛素原的表达，根据特定的要求，在发展中的脊椎动物。
Proinsulin gene expression regulation and function during early embryonic development differ remarkably from those found in postnatal organisms. The embryonic proinsulin protein content decreased from gastrulation to neurulation in contrast with the overall proinsulin messenger RNA increase. This is due to increasing levels of a proinsulin mRNA variant generated by intron 1 retention in the 50 untranslated region. Inclusion of intron 1 inhibited proinsulin translation almost completely without affecting nuclear export or cytoplasmic decay. The novel proinsulin mRNA isoform expression was developmentally regulated and tissue specific. The proportion of intron retention increased from gastrulation to organogenesis, was highest in the heart tube and presomitic region, and could not be detected in the pancreas. Notably, proinsulin addition induced cardiac marker gene expression in the early embryonic stages when the translationally active transcript was expressed. We propose that regulated unproductive splicing and translation is a mechanism that regulates proinsulin expression in accordance with specific requirements in developing vertebrates.