Alternative splicing variants of proinsulin mRNA and the effects of excess proinsulin on cardiac morphogenesis

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• 作者：Enrique Mart¨ªnez-Campos ; Esther Hern¨¢ndez-SanMiguel ; Carmen L¨®pez-S¨¢nchez ; Flora De Pablo ; Catalina Hern¨¢ndez-S¨¢nchez
• 关键词：Proinsulin ; Insulin gene ; Alternative splicing ; Intron retention ; Cardiogenesis ; Cardiac malformation
• 刊名：FEBS Letters
• 出版年：2013
• 出版时间：11 July, 2013
• 年：2013
• 卷：587
• 期：14
• 页码：2272-2277
• 全文大小：1261 K

文摘

Alternative forms of proinsulin mRNA with differential translational capacities and unknown significance are expressed in several developing tissues and in the adult pancreas. In the chick embryo developing heart, we observed low expression of the translationally active transcript of embryonic proinsulin (Pro1B), and predominant expression of the intron 1-unspliced variant, translationally inactive. In the embryonic mouse heart, intron 1-unspliced isoform appeared after E12.5. This tight regulation is required for normal development, since overexpression of Pro1B resulted in abnormal cardiac morphogenesis in 40 % of chick embryos, and was accompanied by changes in gene expression of Amhc1and Vmhc1.